Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding.

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Chappell, Paul 
Meziane, El Kahina 
Harrison, Michael 
Magiera, Łukasz 
Hermann, Clemens 

Highly polymorphic major histocompatibility complex (MHC) molecules are at the heart of adaptive immune responses, playing crucial roles in many kinds of disease and in vaccination. We report that breadth of peptide presentation and level of cell surface expression of class I molecules are inversely correlated in both chickens and humans. This relationship correlates with protective responses against infectious pathogens including Marek's disease virus leading to lethal tumours in chickens and human immunodeficiency virus infection progressing to AIDS in humans. We propose that differences in peptide binding repertoire define two groups of MHC class I molecules strategically evolved as generalists and specialists for different modes of pathogen resistance. We suggest that differences in cell surface expression level ensure the development of optimal peripheral T cell responses. The inverse relationship of peptide repertoire and expression is evidently a fundamental property of MHC molecules, with ramifications extending beyond immunology and medicine to evolutionary biology and conservation.

HIV, MHC, Marek's disease, avian, chicken, human, immunology, peptide repertoire, Acquired Immunodeficiency Syndrome, Adaptive Immunity, Alleles, Amino Acid Sequence, Animals, Antigen Presentation, Binding Sites, Cell Line, Chickens, Crystallography, X-Ray, Gene Expression Regulation, HIV-1, Haplotypes, Herpesvirus 2, Gallid, Histocompatibility Antigens Class I, Marek Disease, Models, Molecular, Molecular Sequence Data, Peptides, Protein Binding, Recombinant Proteins
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eLife Sciences Publications, Ltd
Wellcome Trust (089305/Z/09/Z)
Wellcome Trust Programme grant 089305; Biotechnology and Biological Sciences Research Council (BBSRC) Core Funding to the Pirbright Institute; Biotechnology and Biological Sciences Research Council (BBSRC); Wellcome Trust.