Van Hateren, A., Carter, R., Bailey, A., Kontouli, N., Williams, A.P., Kaufman, J. and Elliott, T.J.
A mechanistic basis for the co-evolution of chicken tapasin and major histocompatibility complex class I (MHC I) proteins
Journal of Biological Chemistry, n/a, . (doi:10.1074/jbc.M113.474031). (PMID:24078633).
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MHC class I molecules display peptides at the cell surface to cytotoxic T cells. The co-factor tapasin functions to ensure MHC I become loaded with high affinity peptides. In most mammals, the tapasin gene appears to have little sequence diversity and few alleles and is located distal to several classical MHC I loci, so tapasin appears to function in a universal way to assist MHC I peptide loading. In contrast the chicken tapasin gene is tightly linked to the single dominantly expressed MHC I locus, is highly polymorphic and moderately diverse in sequence. Therefore tapasin-assisted loading of MHC I in chickens may occur in a haplotype-specific way, via the co-evolution of chicken tapasin and MHC I. Here we demonstrate a mechanistic basis for this co-evolution, revealing differences in the ability of two chicken MHC I alleles to bind and release peptides in the presence or absence of tapasin, where like in mammals efficient self-loading is negatively correlated with tapasin-assisted loading. We found that a polymorphic residue in the MHC I ?3 domain thought to bind tapasin influenced both tapasin function as well as intrinsic peptide-binding properties. Differences were also evident between the MHC alleles in their interactions with tapasin. Lastly we show that a mismatched combination of tapasin and MHC alleles exhibit significantly impaired MHC I maturation in vivo, and that polymorphic MHC residues thought to contact tapasin influence maturation efficiency. Collectively this supports the possibility that tapasin and BF2 proteins have co-evolved resulting in allele-specific peptide-loading in vivo.
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