Surface expression, peptide repertoire and thermostability of chicken class I molecules correlate with peptide transporter specificity
Sowa, Anna K
Hateren, Andy van
Hunt, Lawrence G
Proceedings of the National Academy of Sciences
National Academy of Sciences
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Tregaskes, C., Harrison, M., Sowa, A. K., Hateren, A. v., Hunt, L. G., Vainio, O., & Kaufman, J. (2015). Surface expression, peptide repertoire and thermostability of chicken class I molecules correlate with peptide transporter specificity. Proceedings of the National Academy of Sciences, 113 692-697. https://doi.org/10.1073/pnas.1511859113
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 ten-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 shows 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 due to 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).
ABC transporter, restrictive, permissive, heterozogous advantage, overdominance
This work was originally supported by core funding to the Basel Institute for Immunology (which was founded and supported by F. Hoffmann-La Roche & Co. Ltd., CH-4005 Basel, Switzerland), then by core funding to the Institute for Animal Health [now re-branded the Pirbright Institute, sponsored by the Biotechnology and Biological Sciences Research Council (BBSRC) of the UK] and finally by programme grant 089305 from the Wellcome Trust to JK.
Wellcome Trust (089305/Z/09/Z)
External DOI: https://doi.org/10.1073/pnas.1511859113
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253011