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- W4210312669 abstract "HLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that are both found at a high frequency in all human populations, and yet they only differ by one residue on the alpha2 helix (B*4402 Asp156-->B*4403 Leu156). CTLs discriminate between HLA-B*4402 and B*4403, and these allotypes stimulate strong mutual allogeneic responses reflecting their known barrier to hemopoeitic stem cell transplantation. Although HLA-B*4402 and B*4403 share >95% of their peptide repertoire, B*4403 presents more unique peptides than B*4402, consistent with the stronger T cell alloreactivity observed toward B*4403 compared with B*4402. Crystal structures of B*4402 and B*4403 show how the polymorphism at position 156 is completely buried and yet alters both the peptide and the heavy chain conformation, relaxing ligand selection by B*4403 compared with B*4402. Thus, the polymorphism between HLA-B*4402 and B*4403 modifies both peptide repertoire and T cell recognition, and is reflected in the paradoxically powerful alloreactivity that occurs across this minimal mismatch. The findings suggest that these closely related class I genes are maintained in diverse human populations through their differential impact on the selection of peptide ligands and the T cell repertoire. PMID: 12939341 Funding information This work was supported by: Wellcome Trust, United Kingdom" @default.
- W4210312669 created "2022-02-08" @default.
- W4210312669 creator A5074802230 @default.
- W4210312669 date "2003-09-10" @default.
- W4210312669 modified "2023-10-05" @default.
- W4210312669 title "Faculty Opinions recommendation of A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition." @default.
- W4210312669 doi "https://doi.org/10.3410/f.1015306.196306" @default.
- W4210312669 hasPublicationYear "2003" @default.
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