A mechanistic basis for the co-evolution of chicken tapasin and major histocompatibility complex class I (MHC I) proteins.
MHC class I molecules display peptides at the cell surface to cytotoxic T cells. The co-factor tapasin functions to ensure that MHC I becomes 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 and 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, as in mammals, efficient self-loading is negatively correlated with tapasin-assisted loading. We found that a polymorphic residue in the MHC I α3 domain thought to bind tapasin influenced both tapasin function and intrinsic peptide binding properties. Differences were also evident between the MHC alleles in their interactions with tapasin. Last, 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.
From the Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton SO16 6YD, United Kingdom,; the Institute for Animal Health, Compton RG20 7NN, United Kingdom.
Andy
A
van Hateren
From the Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton SO16 6YD, United Kingdom.
Rachel
R
Carter
From the Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton SO16 6YD, United Kingdom.
Alistair
A
Bailey
From the Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton SO16 6YD, United Kingdom.
Nasia
N
Kontouli
From the Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton SO16 6YD, United Kingdom.
Anthony P
AP
Williams
the Institute for Animal Health, Compton RG20 7NN, United Kingdom; the Departments of Pathology and Veterinary Medicine, University of Cambridge, Cambridge CB2 1QP, United Kingdom. Electronic address: jfk31@cam.ac.uk.
Jim
J
Kaufman
From the Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton SO16 6YD, United Kingdom,. Electronic address: tje@soton.ac.uk.
Tim
T
Elliott
D000483:Alleles; D000818:Animals; D002645:Chickens; D019143:Evolution, Molecular; D056426:Genetic Loci / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000276:immunology; D017434:Protein Structure, Tertiary
D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; C107762:tapasin
Antigen Presentation; Chicken MHC; Co-evolution; Evolution; Immunology; Major Histocompatibility Complex (MHC); Peptide Selection; Protein-Protein Interactions; Tapasin