title: Surface expression, peptide repertoire, and thermostability of chicken class I molecules correlate with peptide transporter specificity.
abstract: The chicken major histocompatibility complex (MHC) has strong genetic associations with resistance and susceptibility to certain infectious pathogens. The cell surface expression level of MHC class I molecules varies as much as 10-fold between chicken haplotypes and is inversely correlated with diversity of peptide repertoire and with resistance to Marek's disease caused by an oncogenic herpesvirus. Here we show that the average thermostability of class I molecules isolated from cells also varies, being higher for high-expressing MHC haplotypes. However, we find roughly the same amount of class I protein synthesized by high- and low-expressing MHC haplotypes, with movement to the cell surface responsible for the difference in expression. Previous data show that chicken TAP genes have high allelic polymorphism, with peptide translocation specific for each MHC haplotype. Here we use assembly assays with peptide libraries to show that high-expressing B15 class I molecules can bind a much wider variety of peptides than are found on the cell surface, with the B15 TAPs restricting the peptides available. In contrast, the translocation specificity of TAPs from the low-expressing B21 haplotype is even more permissive than the promiscuous binding shown by the dominantly expressed class I molecule. B15/B21 heterozygote cells show much greater expression of B15 class I molecules than B15/B15 homozygote cells, presumably as a result of receiving additional peptides from the B21 TAPs. Thus, chicken MHC haplotypes vary in several correlated attributes, with the most obvious candidate linking all these properties being molecular interactions within the peptide-loading complex (PLC).
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom;
authors.forename: Clive A
authors.initials: CA
authors.lastname: Tregaskes
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom;
authors.forename: Michael
authors.initials: M
authors.lastname: Harrison
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom;
authors.forename: Anna K
authors.initials: AK
authors.lastname: Sowa
authors.affiliation: Division of Immunology, Institute for Animal Health, Compton RG20 7NN, United Kingdom;
authors.forename: Andy
authors.initials: A
authors.lastname: van Hateren
authors.affiliation: Division of Immunology, Institute for Animal Health, Compton RG20 7NN, United Kingdom;
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hunt
authors.affiliation: Basel Institute for Immunology, Basel CH-4005, Switzerland; Department of Medical Microbiology, University of Oulu and Nordlab, Oulu FI-90014, Finland;
authors.forename: Olli
authors.initials: O
authors.lastname: Vainio
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; Division of Immunology, Institute for Animal Health, Compton RG20 7NN, United Kingdom; Basel Institute for Immunology, Basel CH-4005, Switzerland; Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom jfk31@cam.ac.uk.
authors.forename: Jim
authors.initials: J
authors.lastname: Kaufman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D002645:Chickens; D000939:Epitopes / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D006239:Haplotypes; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006720:Homozygote; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D055550:Protein Stability; D013379:Substrate Specificity; D013696:Temperature; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D010455:Peptides; D001613:beta 2-Microglobulin; C043912:peptide permease
keywords: ABC transporter; heterozygous advantage; overdominance; permissive; restrictive