Antigen presentation to CD8+ T cells by MHC class I molecules is essential for host defense against viral infections. Various mechanisms have evolved in multiple viruses to escape immune surveillance and defense to support viral proliferation in host cells. Through in vitro SARS‐CoV‐2 infection studies and analysis of COVID‐19 patient samples, we found that SARS‐CoV‐2 suppresses the induction of the MHC class I pathway by inhibiting the expression and function of NLRC5, a major transcriptional regulator of MHC class I genes. (...) In this review, we discuss the molecular mechanisms for suppression of the MHC class I pathway and clinical implications for COVID‐19. (shrink)

The role of the major histocompatibility complex (MHC) in mate choice in humans is controversial. Nowadays, the availability of genetic variation data at genomic scales allows for a careful assessment of this question. In 2008, Chaix et al. reported evidence for MHC‐dependent mate choice among European American spouses from the HapMap 2 dataset. Recently, Derti et al. suggested that this observation was not robust. Furthermore, when Derti et al. applied similar analyses to the HapMap 3 European American samples, they did (...) not see a significant effect. Although some of the points raised by Derti et al. are relevant, we disagree with the reported absence of evidence for MHC‐dependent mate choice within the HapMap samples. More precisely, we show here that the MHC dissimilarity among HapMap 3 European American spouses is still extreme in comparison to the rest of the genome, even after multiple testing correction. This finding supports the hypothesis of MHC‐dependent mate choice in some human populations. (shrink)

Receptors on cytotoxic T lymphocytes and natural killer cells play well‐established roles in the immunological response and share a common ligand in the form of MHC‐I. We discuss how a variety of MHC‐I receptors are also expressed on myelomonocytic cells such as macrophages and dendritic cells. Since myelomonocytic MHC‐I receptors recognise a broad range of alleles and MHC‐I structures, we propose that their task is to discern expression levels and folding forms of MHC. We describe a model in which these (...) recognition events would regulate bidirectional cross talk between cells of innate and adaptive immune systems to organise an ongoing combined immune response. We discuss how such a model is supported by recent literature and might function in a variety of contexts, including immunoregulation during pregnancy. Our model also offers an alternative explanation of immune dysregulation rather than autoimmunity during HLA‐B27‐associated spondyloarthropathies and addresses a number of conundrums in this field. BioEssays 27: 542–550, 2005. © 2005 Wiley periodicals, Inc. (shrink)

Current models for T‐cell recognition of foreign antigen depict the T‐cell receptor as having a single antibody‐like combining site which binds a complex of MHC and antigen. An alternative hypothesis is presented here; it is proposed that the first domains of the MHC function as inverted V‐like regions to complement the TcR V‐regions in creating antigen binding sites.

Graphical AbstractMHC II, a major feature of the adaptive immune system, is lacking in Atlantic cod, and there are different scenarios (metabolic cost hypothesis or functional shift hypothesis) that might explain this loss. The lack of MHC II coincides with an increased number of genes for MHC I and Toll-like receptors (TLRs).

Soma‐to‐germline feedback is forbidden under the neo‐Darwinian paradigm. Nevertheless, there is a growing realization it occurs frequently in immunoglobulin (Ig) variable (V) region genes. This is a surprising development. It arises from a most unlikely source in light of the exposure of co‐author EJS to the haplotype data of RL Dawkins and others on the polymorphism of the Major Histocompatibility Complex, which is generally assumed to be the most polymorphic region in the genome (spanning ∼4 Mb). The comparison between the (...) magnitude of MHC polymorphism with estimates for the human heavy chain immunoglobulin V locus (spanning ∼1 Mb), suggests IGHV could be many orders of magnitude more polymorphic than the MHC. This conclusion needs airing in the literature as it implies generational churn and soma‐to‐germline gene feedback. Pedigree‐based experimental strategies to resolve the IGHV issue are outlined. (shrink)

Major histocompatibility complex (MHC)‐associated mate choice is thought to give offspring a fitness advantage through disease resistance. Primates offer a unique opportunity to understand MHC‐associated mate choice within our own zoological order, while their social diversity provides an exceptional setting to examine the genetic determinants and consequences of mate choice in animal societies. Although mate choice is constrained by social context, increasing evidence shows that MHC‐dependent mate choice occurs across the order in a variety of socio‐sexual systems and favours mates (...) with dissimilar, diverse or specific genotypes non‐exclusively. Recent research has also identified phenotypic indicators of MHC quality. Moreover, novel findings rehabilitate the importance of olfactory cues in signalling MHC genes and influencing primate mating decisions. These findings underline the importance to females of selecting a sexual partner of high genetic quality, as well as the generality of the role of MHC genes in sexual selection. (shrink)

Cancer is generally defined as uncontrollable growth of cells caused by genetic aberrations and/or environmental factors. Yet contagious cancers also occur. The recent emergence of a contagious cancer in Tasmanian devils has reignited interest in transmissible cancers. Two naturally occurring transmissible cancers are known: devil facial tumour disease and canine transmissible venereal tumour. Both cancers evolved once and have then been transmitted from one individual to another as clonal cell lines. The dog cancer is ancient; having evolved more than 6,000 (...) years ago, while the devil disease was first seen in 1996. In this review I will compare and contrast the two diseases focusing on the life histories of the clonal cell lines, their evolutionary trajectories and the mechanisms by which they have achieved immune tolerance. A greater understanding of these contagious cancers will provide unique insights into the role of the immune system in shaping tumour evolution and may uncover novel approaches for treating human cancer. (shrink)

”Meaningful human control” is a term invented in the political and legal debate on autonomous weapons system, but it is nowadays also used in many other contexts. It is supposed to specify conditions under which an artificial system is under the right kind of control to avoid responsibility gaps: that is, situations in which no moral agent is responsible. Santoni de Sio and Van den Hoven have recently suggested a framework that can be used by system designers to operationalize this (...) kind of control. It is the purpose of this paper to facilitate further operationalization of ”meaningful human control”. -/- This paper consists of two parts. In the first part I resolve an ambiguity that plagues current operationalizations of MHC. One of the design conditions says that the system should track the reasons of the relevant agents. This condition is ambiguous between the kind of reasons involved. On one interpretation it says that a system should track motivating reasons, while it is concerned with normative reasons on the other. Current participants in the debate interpret the framework as being concerned with (something in the vicinity of) motivating reasons. I argue against this interpretation by showing that meaningful human control requires that a system tracks normative reasons. Moreover, I maintain that an operationalization of meaningful human control that fails to track the right kind of reasons is morally problematic.When this is properly understood, it can be shown that the framework of MHC is committed to the agent-relativity of reasons. More precisely, I argue in the second part of this paper that if the tracking condition of MHC plays an important role in responsibility attribution (as the proponents of the view maintain), then the framework is incompatible with first-order normative theories that hold that normative reasons are agent-neutral (such as many versions of consequentialism). In the final section I present three ways forward for the proponent of MHC as reason-responsiveness. (shrink)

The increasing complexity and ubiquity of autonomously operating artificially intelligent (AI) systems call for a robust theoretical reconceptualization of responsibility and control. The Meaningful Human Control (MHC) approach to the design and operation of AI systems provides such a framework. However, in its focus on accountability and minimizing harms, it neglects how we may flourish in interaction with such systems. In this chapter, I show how the MHC framework can be expanded to meet this challenge by drawing on the ethics (...) of carebots and embodied design. First, I examine how discussions about flourishing with carebots invite us to consider the extent to which we control our moral character Second, I argue that we can understand the cultivation of moral character in terms of embodied virtues arising from operating in particular ecologies. Third, I demonstrate how this analysis fruitfully informs the design of carebots as supporting reciprocity and empathy. (shrink)

The international debate on the ethics and legality of autonomous weapon systems (AWS), along with the call for a ban, primarily focus on the nebulous concept of fully autonomous AWS. These are AWS capable of target selection and engagement absent human supervision or control. This paper argues that such a conception of autonomy is divorced from both military planning and decision-making operations; it also ignores the design requirements that govern AWS engineering and the subsequent tracking and tracing of moral responsibility. (...) To show how military operations can be coupled with design ethics, this paper marries two different kinds of meaningful human control (MHC) termed levels of abstraction. Under this two-tiered understanding of MHC, the contentious notion of ‘full’ autonomy becomes unproblematic. (shrink)

In this paper we define an augmentation mHC of the Heyting propositional calculus HC by a modal operator ?. This modalized Heyting calculus mHC is a weakening of the Proof-Intuitionistic Logic KM of Kuznetsov and Muravitsky. In Section 2 we present a short selection of attractive (algebraic, relational, topological and categorical) features of mHC. In Section 3 we establish some close connections between mHC and certain normal extension K4.Grz of the modal system K4. We define a translation of mHC into (...) K4.Grz and prove that this translation is exact, i. e. theorem-preserving and deducibility-invariant. We have established (however, in this note we do not present a proof of this) that the lattice of all extensions of mHC is isomorphic to the lattice of normal extensions of K4.Grz (a generalization of the Kuznetsov and Muravitsky theorem). (shrink)

All around the world in March, due to COVID-19, competitive sport calendars were suddenly canceled, jeopardizing the training programs of athletes. Moreover, in Italy, the government banned all non-essential travel across the entire country from the beginning of March. Consequently, Italian cyclists were banned from leaving their homes and therefore unable to perform their ordinary training activities. The Italian Association of Professional Cyclists early on during that period noticed that several cyclists were experiencing a worrying decrease in their mental well-being (...) and asked the authors to set up an online Sport Psychology Intervention during lockdown to enhance the athletes' mental health. Through a number of unprecedented events and considerations, the aim of the current investigation was to assess the Italian cyclists' mental health during the lockdown and its changes after the SPI. We validated the Italian version of the Sport Mental Health Continuum Short Form —presented in Study 1—and then applied it to a sample of Italian professional cyclists—presented in Study 2—prior to and after the SPI. To achieve these objectives, the reliability and construct validity of the Italian version of the Sport MHC-SF were tested in Study 1. RM-MANOVA tests were run to evaluate the effect of SPI on cyclists in Study 2. A total of 185 Italian athletes were involved in the validation of the MHC in Study 1 and 38 professional cyclists in Study 2. Results from Study 1 suggested a three-factor higher order model of Sport MHC-SF [Model fit: χ2 = 471.252, p < 0.000; CFI = 0.951; RMSEA = 0.049; RMR= 0.048]. MCFA showed that the default model kept invariance among groups of athletes. Results from Study 2 highlighted that professional cyclists who followed the SPI were able to cope better with psychological stressors, showing improved well-being compared to the athletes that did not. No significant differences were found for emotional and social well-being. The present multi-study paper contributes to the theoretical field with a validated measure of Sport MHC-SF translated in the Italian language and culture. It also provides practical implications related to cases of reduced mental health due to injury, illness, or similar situations of home confinement in the future. (shrink)

Introduction. Eating Disorders (EDs) are serious psychiatric disorders, impacting physical and psychosocial functioning, often with a chronic course and high mortality rates. The two continua model of mental health states that mental health is a complete state, that is not merely the absence of mental illness, but also the presence of mental health. This model was studied among ED patients by comparing the levels of well-being to the Dutch general population and by examining the of well-being and psychopathology. Method. A (...) total of 468 female ED patients participated in this study during application and intake at a specialized ED treatment centre in the Netherlands. They filled out questionnaires about well-being (MHC-SF), general psychopathology (OQ-45), and ED psychopathology (EDE-Q). Categorical and mean well-being levels were calculated. Also, the correlates of these variables were examined with Pearson correlation and multiple hierarchical regression analysis. Results. ED patients showed lower levels of emotional, psychological and social well-being on average compared to the general population. About 26% of the ED patients experienced low levels of well-being (languishing). However, also 13% experienced high levels of well-being (flourishing), varying between 9% in Anorexia Nervosa to 25% in Binge Eating Disorder. ED psychopathology and general well-being showed a moderate negative correlation. For patients with Bulimia Nervosa and Binge Eating Disorder however no such correlation was found. Lower general psychopathology, not having a history of hospitalization for the ED, and adaptive personal functioning were correlated with well-being among ED patients. Conclusion This study shows initial support for the two continua model of mental health among ED patients. Psychopathology and well-being should be considered as related, but distinct dimensions of mental health in ED patients. Further research should focus on the possible reciprocal relationships between psychopathology and well-being during recovery. It is recommended to monitor well-being during treatment and to implement interventions for well-being to realize complete recovery for those patients with inadequate levels of well-being. (shrink)

The immune surveillance theory postulates that spontaneous tumors are normally rejected by the immune system and appear only when they override host‐immune recognition and rejection mechanisms. The present mini‐review describes a spontaneous tumor system, the reticulum cell sarcomas (RCS) in SJL/J mice, that is dependent on host tumor‐specific immune lymphocytes for growth. This continuous tumor‐specific response results in tumor progression and death of the host. This tumor system contradicts the basic concept of immune surveillance. We propose as an explanation that (...) some highly antigenic tumors, like the RCS, may have evolved in a non‐autonomous fashion but, nevertheless, have lost regulatory controls of cell proliferation. In the RCS system, the tumor expresses Class II MHC I‐E like specificities that are not expressed on the host cells and which selectively stimulate a subpopulation of I‐E specific T cells, the Vβ17a+ clonotype, leading to their expansion and continuous nurturing of the tumor via secreted lymphokines. This neoantigenic stimulation bypasses the tumor regulatory response that might have resulted if the tumor had not expressed neo‐antigens. Furthermore, passive administration of anti‐clonotypic antibody to tumor‐bearing mice results in tumor regression and long‐term survival through removal of the tumor reactive T cells. Thus, in this tumor system, immunosuppressive treatments are the prescription for tumor rejection. (shrink)

The human major histocompatibility complex (MHC), on the short arm of chromosome 6, represents one of the most extensively characterised regions of the human genome. This ∼4 Mb segment of DNA contains genes encoding the polymorphic MHC class I and class II molecules which are involved in antigen presentation during an immune response. Recently the whole of the MHC has been cloned in cosmids and/or yeast artificial chromosomes (YACs) and large portions have been characterised for the presence of novel genes. (...) Many unrelated genes, both housekeeping and tissue specific, have been identified and the gene density in some regions is now approaching one gene every few kilobases. Some of the novel genes encode proteins involved in the intracellular processing and transport of antigens that are presented by MHC class I molecules. Others, however, have no obvious role in the immune response. The MHC is located in the chromosome band 6p21.3 which is a Giemsa (G)‐light band. The detection of such a large number of functional genes (at least 70) in this region is compatible with the idea that both housekeeping and tissue‐specific genes are localised predominantly in G‐light bands. (shrink)

The molecular components of complement are a major part of the armoury of the mammalian immune system, being required for the lysis of antibody‐targeted cells. Several of the complement proteins are known to be encoded by genes within the major histocompatibility complex (MHC). Molecular analysis of these genes is providing new information on the basis of complement action and the possible roles of this system in autoimmune disease.

I‐J has been regarded as a polymorphic genetic marker controlled by a locus in the major histocompatibility complex (MHC) which is expressed only on functional T cells. However, this antigenic determinant has been found not to be directly encoded by the MHC gene per se but is somatically generated according to the MHC of the cellular environment during ontogeny. This explains the apparent linkage of I‐J to MHC, despite the failure to find the structural gene for I‐J within the MHC. (...) The I‐J paradox provides an instance of a polymorphism that does not follow the standard genetics of Mendelian structural genes. (shrink)

The Westermarck effect (sexual inhibition among individuals raised together) is argued to be mediated olfactorily. Various animals, including humans, distinguish among individuals by scent (significantly determined by MHC genotype), and some avoid cosocialized associates on this basis. Possible models of olfactory mechanisms in humans are evaluated. Evidence suggests aversions develop during an early sensitizing period, attach to persons as much as to their scents, and are more powerful among females than among males. Adult to child aversions may develop similarly, but (...) more likely result from stimulus generalization. This hypothesis accords with current evidence and yields testable predictions (e.g., anosmia will prevent inhibition) that, should they be supported, will conclusively ground the Westermarck effect in a biological mechanism. (shrink)

The international debate on the ethics and legality of autonomous weapon systems (AWS) as well as the call for a ban are primarily focused on the nebulous concept of fully autonomous AWS. More specifically, on AWS that are capable of target selection and engagement without human supervision or control. This thesis argues that such a conception of autonomy is divorced both from military planning and decision-making operations as well as the design requirements that govern AWS engineering and subsequently the tracking (...) and tracing of moral responsibility. To do this, this thesis marries two different levels of meaningful human control (MHC), termed levels of abstraction, to couple military operations with design ethics. In doing so, this thesis argues that the contentious notion of ‘full’ autonomy is not problematic under this two-tiered understanding of MHC. It proceeds to propose the value sensitive design (VSD) approach as a means for designing for MHC. (shrink)

Artificial intelligence is currently changing many areas of society. Especially in health, where critical decisions are made, questions of control must be renegotiated: who is in control when an automated system makes clinically relevant decisions? Increasingly, the concept of meaningful human control (MHC) is being invoked for this purpose. However, it is unclear exactly how this concept is to be understood in health. Through a systematic review, we present the current state of the concept of MHC in health. The results (...) show that there is not yet a robust MHC concept for health. We propose a broader understanding of MHC along three strands of action: enabling, exercising and evaluating control. Taking into account these strands of action and the established rules and processes in the different health sectors, the MHC concept needs to be further developed to avoid falling into two gaps, which we have described as theoretical and labelling gaps. (shrink)

We present the design goals and metatheory of the Monadic Hybrid Calculus, a new formal system that has the same power as the Monadic Predicate Calculus. MHC allows quantification, including relative quantification, in a straightforward way without the use of bound variables, using a simple adaptation of modal logic notation. Thus “all Greeks are mortal” can be written as [G]M. MHC is also ‘hybrid’ in that it has individual constants, which allow us to formulate statements about particular individuals. Thus “Socrates (...) is Athenian and mortal” can be formalised as s.For our proof system, we use a simple adaptation of Beth-style tableaus. The availability of individual constants eliminates the need for labelled deduction.We discuss first the pragmatic and pedagogical advantages of MHC. Then we present the metatheory: formal syntax, semantics, proof rules, soundness, completeness and expressive equivalence with the Monadic Predicate Calculus. (shrink)

The T lymphocyte receptor for antigen, which operates in conjunction with gene products of the major histocompatibility complex (MHC), is a molecular complex comprised of five polypeptide chains. Both the 49 kDa alpha and 43 kDa beta chains are immunoglobulin‐like and thus contain variable domains responsible for ligand binding. In contrast, the 20–25 kDa T3 gamma, delta and epsilon chains are monomorphic structures presumably involved in transmembrane signalling. The alpha and beta subunits are disulfide bonded to each other and held (...) in noncovalent association with the T3 chains. T3‐Ti receptor crosslinking leads to conformational modification of a second T lineage specific molecule, termed the 50 kDa T11 structure which in turn leads to protein kinase C activation, elevation in intracytoplasmic free calcium and Na+/H+ antiport stimulation. (shrink)

Central nervous system (CNS)Abbreviations: CNS=central nervous system; PNS=peripheral nervous system; MS=multiple sclerosis; MBP=myelin basic protein; MHC=major histocompatibility complex; EAE=experimental allergic encephalomyelitis; O‐2A=oligodendrocyte‐type 2 astrocyte; GC=galactocerebroside; GFAP=glial fibrillary acidic protein; FGF=fibroblast growth factor; IGF1=insulin‐like growth factor. regeneration is a subject of great interest, particularly in diseases causing a dramatic loss of neurons. However, some CNS diseases do not affect neurons but damage other cells, such as the myelin‐forming cells — called oligodendrocytes — which are also crucial to the harmonious function of (...) the nervous system. Diseases in which oligodendrocytes and myelin are attacked can cause devastating neurological dysfunction which is sometimes followed by recovery and myelin repair or remyelination. The question of the regeneration potential of oligodendrocytes in experimental and human demyelinating diseases such as multiple sclerosis has been debated for a long time. Present evidence suggests that oligodendrocyte precursor cells persist in the adult CNS and that oligodendrocyte regeneration can occur but may be limited by ongoing disease processes. Here we will briefly review recent advances which have broadened our understanding of the cellular and molecular events of CNS remyelination. (shrink)

Adaptive immunity is unique to the vertebrates, and the molecules involved (including immunoglobulins, T cell receptors and the major histocompatibility complex molecules) seem to have diversified very rapidly early in vertebrate history. Reconstruction of gene phylogenies has yielded insights into the evolutionary origin of a number of molecular systems, including the complement system and the major histocompatibility complex (MHC). These analyses have indicated that the C5 component of complement arose by gene duplication prior to the divergence of C3 and C4, (...) which suggests that the alternative complement pathway was the first to evolve. In the case of the MHC, phylogenetic analysis supports the hypothesis that MHC class II molecules evolved before class I molecules. The fact that the MHC‐linked proteasome components that specifically produce peptides for presentation by class I MHC appear to have originated before the separation of jawed and jawless vertebrates suggests that the MHC itself may have been present at this time. Immmune system gene families have evolved by gene duplication, interlocus recombination and (in some cases) positive Darwinian selection favoring diversity at the amino acid level. (shrink)

The expression of products encoded by the major histocompatibility complex (MHC) on tumor cells has recently been studied extensively. It has been found that many malignant tumor cells have their MHC antigens ‘switched‐off’ but that these antigens are re‐expressed following DNA‐mediated gene transfer, with increased tumor immunogenicity as a result and the consequence that these ‘transformed’ tumor cells are rejected in vivo.: This review will discuss approaches that have been taken to induce strong tumor‐specific immunity by the manipulation of MHC (...) expression on tumor cells. (shrink)

The dual-continua model of mental health provides a contemporary framework for conceptualising and operationalising mental health. According to this model, mental health is distinct from but related to mental illness, and not the opposite or merely the absence of psychopathology symptoms. To examine the validity of the dual-continua model, previous studies have either applied variable-based analysis such as confirmatory factor analysis, or used predetermined cut-off points for subgroup division. The present study extends this contribution by subjecting data from an African (...) sample to both CFA and latent class analysis to test the dual-continua model in Africa. We applied CFA separately for the Mental Health Continuum—Short Form and Patient Health Questionnaire—9 ; and LCA on combined item responses. College students from Ghana, Kenya, Mozambique, and South Africa completed the MHC-SF and PHQ-9. With minor modifications to the measurement models, the CFA results of this study confirm the three-factor structure of the MHC-SF, and a unidimensional solution for the PHQ-9. LCA results show the presence of three distinct latent classes: languishing with moderate endorsement of depressive symptoms, flourishing with low endorsement of depressive symptoms, and moderate mental health with high endorsement of depressive symptoms. These findings further contribute to affirming the evidence for the dual-continua model of mental health, with implications for the assessment of mental health, to inform policy, practise, and future research in community and clinical settings in Africa. (shrink)

A Chair of the Philosophy Department at a local college explains his reasoning and tactics on how he transferred knowledge from teacher to student for his newly created course, “Philosophy for Children” at MHC.

A Chair of the Philosophy Department at a local college explains his reasoning and tactics on how he transferred knowledge from teacher to student for his newly created course, “Philosophy for Children” at MHC.

In circulation, T cells are spherical with selectin enriched dynamic microvilli protruding from the surface. Following extravasation, these microvilli serve another role, continuously surveying their environment for antigen in the form of peptide‐MHC (pMHC) expressed on the surface of antigen presenting cells (APCs). Upon recognition of their cognate pMHC, the microvilli are initially stabilized and then flatten into F‐actin dependent microclusters as the T cell spreads over the APC. Within 1–5 min, clathrin is recruited by the ESCRT‐0 component Hrs to (...) mediate release of T cell receptor (TCR) loaded vesicles directly from the plasma membrane by clathrin and ESCRT‐mediated ectocytosis (CEME). After 5‐10 min, Hrs is displaced by the endocytic clathrin adaptor epsin‐1 to induce clathrin‐mediated trans‐endocytosis (CMTE) of TCR‐pMHC conjugates. Here we discuss some of the functional properties of the clathrin machinery which enables it to control these topologically opposite modes of membrane transfer at the immunological synapse, and how this might be regulated during T cell activation. (shrink)

Observations suggesting the existence of natural antibody prior to exposure of an organism to the corresponding antigen, led to the natural selection theory of antibody formation of Jerne in 1955, and to the two signal hypothesis of Forsdyke in 1968. Aspects of these were not only first discoveries but also foundational discoveries in that they influenced contemporaries in a manner that, from our present vantage point, appears to have been constructive. Jerne’s later hypothesis (1971, European Journal of Immunology 1: 1–9), (...) that antibody-like receptors on lymphocytes were selected over evolutionary time for reactivity with the major histocompatibility complex (MHC) antigens of the species, was a first, but it was incorrect, and was foundational only to the extent that it emphasized the need to explain the Simonsen phenomenon. Although easily construed as derivative of Jerne (1971), the affinity/avidity model of Forsdyke (1975, Journal of Theoretical Biology 52: 187–198), which predicted that cell-surface components, including MHC antigens, would restrict antigen-reactivity by somatically shaping lymphocyte repertoires, was actually an extension of the two signal hypothesis. While presenting a mechanism for the positive selection of lymphocyte repertoires, and explaining the Simonsen phenomenon, the affinity/avidity model was not foundational in that it had to be independently rediscovered. For science to advance optimally we must seek to close temporal gaps so that first discoveries are also foundational. Listening to young scientists may be part of the solution. (shrink)

A Chair of the Philosophy Department at a local college explains his reasoning and tactics on how he transferred knowledge from teacher to student for his newly created course, “Philosophy for Children” at MHC.

I argue that population-level selection does not necessarily have to be invoked to explain the polymorphism at the MHC locus. I argue that the authors' attempt to model operant conditioning in Darwinian terms faces a serious problem. Depending on how many operant responses we take to comprise a sequence, different conclusions about whether or not evolution is occurring in an operant lineage will be reached.

The immune system distinguishes between two types of antigenic sites: one of these binds to immunoglobulins (IgGs) (i.e. antibodies), while the other binds to receptor molecules on T lymphocytes (i.e. the T‐cell receptors (TcRs)). The latter interaction occurs only when the antigen is presented in association with a self‐transplantation antigen, a so‐called MHC‐restriction element. This article discusses what is known about the structure of antigenic sites and their molecular interactions with antibodies, MHC‐restriction elements, and T‐lymphocyte receptors.

In contrast to the views put forth by Stein & Glasier, we support the use of inbred strains of rodents in studies of the immunobiology of neural transplants. Inbred strains demonstrate homology of the major histocompatibility complex (MHC). Virtually all experimental work in transplantation immunology is performed using inbred strains, yet very few published studies of immune rejection in intracerebral grafts have used inbred animals.

T lymphocytes circulate continually throughout the peripheral lymphoid organs, where they scrutinize the surface of cells to detect the presence of nonself protein fragments. During the last years, many facets of T-cell function have been unravelled. After being bound by major histocompatibility complex (MHC) molecules, peptides derived from nonself as well as from self proteins are delivered to the cell surface. A few copies of a nonself peptide “presented” at the cell surface in the context of an MHC molecule can (...) be detected by specific T cells, and suffice to trigger T-cell activation. This paper reviews the requirements imposed on T cells to fulfill this exquisite sensitivity. BioEssays 20:412–422, 1998.© 1998 John Wiley & Sons Inc. (shrink)

T lymphocytes circulate continually throughout the peripheral lymphoid organs, where they scrutinize the surface of cells to detect the presence of nonself protein fragments. During the last years, many facets of T-cell function have been unravelled. After being bound by major histocompatibility complex (MHC) molecules, peptides derived from nonself as well as from self proteins are delivered to the cell surface. A few copies of a nonself peptide “presented” at the cell surface in the context of an MHC molecule can (...) be detected by specific T cells, and suffice to trigger T-cell activation. This paper reviews the requirements imposed on T cells to fulfill this exquisite sensitivity. BioEssays 20:412–422, 1998.© 1998 John Wiley & Sons Inc. (shrink)

Observations suggesting the existence of natural antibody prior to exposure of an organism to the corresponding antigen, led to the natural selection theory of antibody formation of Jerne in 1955, and to the two signal hypothesis of Forsdyke in 1968. Aspects of these were not only first discoveries but also foundational discoveries in that they influenced contemporaries in a manner that, from our present vantage point, appears to have been constructive. Jerne's later hypothesis (1971, European Journal of Immunology 1: 1-9), (...) that antibody-like receptors on lymphocytes were selected over evolutionary time for reactivity with the major histocompatibility complex (MHC) antigens of the species, was a first, but it was incorrect, and was foundational only to the extent that it emphasized the need to explain the Simonsen phenomenon. Although easily construed as derivative of Jerne (1971), the affinity/avidity model of Forsdyke (1975, Journal of Theoretical Biology 52: 187-198), which predicted that cell-surface components, including MHC antigens, would restrict antigen-reactivity by somatically shaping lymphocyte repertoires, was actually an extension of the two signal hypothesis. While presenting a mechanism for the positive selection of lymphocyte repertoires, and explaining the Simonsen phenomenon, the affinity/avidity model was not foundational in that it had to be independently rediscovered. For science to advance optimally we must seek to close temporal gaps so that first discoveries are also foundational. Listening to young scientists may be part of the solution. (shrink)