title: Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding.
abstract: 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.
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors: Paul
authors: P
authors: Chappell
authors: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: El Kahina
authors: el K
authors: Meziane
authors: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: Michael
authors: M
authors: Harrison
authors: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: Łukasz
authors: Ł
authors: Magiera
authors: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: Clemens
authors: C
authors: Hermann
authors: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: Laura
authors: L
authors: Mears
authors: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: Antony G
authors: AG
authors: Wrobel
authors: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: Charlotte
authors: C
authors: Durant
authors: Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Lise Lotte
authors: LL
authors: Nielsen
authors: Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Søren
authors: S
authors: Buus
authors: Target Discovery Institute, University of Oxford, Oxford, United Kingdom.
authors: Nicola
authors: N
authors: Ternette
authors: Pirbright Institute, Compton, United Kingdom.
authors: William
authors: W
authors: Mwangi
authors: Pirbright Institute, Compton, United Kingdom.
authors: Colin
authors: C
authors: Butter
authors: Pirbright Institute, Compton, United Kingdom.
authors: Venugopal
authors: V
authors: Nair
authors: Anthony Nolan Research Institute, The Royal Free Hospital, London, United Kingdom.
authors: Trudy
authors: T
authors: Ahyee
authors: Anthony Nolan Research Institute, The Royal Free Hospital, London, United Kingdom.
authors: Richard
authors: R
authors: Duggleby
authors: Anthony Nolan Research Institute, The Royal Free Hospital, London, United Kingdom.
authors: Alejandro
authors: A
authors: Madrigal
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors: Pietro
authors: P
authors: Roversi
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors: Susan M
authors: SM
authors: Lea
authors: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: Jim
authors: J
authors: Kaufman
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D056704:Adaptive Immunity; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001665:Binding Sites; D002460:Cell Line; D002645:Chickens; D018360:Crystallography, X-Ray; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000276:immunology; D006239:Haplotypes; D008381:Herpesvirus 2, Gallid / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008380:Marek Disease / Q000276:immunology* / Q000821:virology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011994:Recombinant Proteins
keywords: HIV; MHC; Marek's disease; avian; chicken; human; immunology; peptide repertoire