The Bw4/Bw6 difference between HLA-B0802 and HLA-B0801 changes the peptides endogenously bound and the stimulation of alloreactive T cells (original) (raw)

Abstract

HLA-B*0801 is unique among HLA-B allotypes in having dominant amino acid anchors at positions 3 and 5 of the peptide-binding motif. HLA-B*0802 is a variant of HLA-B*0801 in which the Bw6 sequence motif is replaced by a Bw4 sequence motif. This change, involving substitutions at positions 77, 80, 81, 82, and 83 of the B*08 heavy chain, is probably the result of a single evolutionary event of interallelic conversion. Moreover, the difference between B*0802 and B*0801 is sufficient to stimulate a cytotoxic T-cell response. To assess further the functional impact of the Bw4 motif on a B8 background, we compared the peptide-binding specificity of the B*0801 and B*0802 allotypes by sequencing the mixture of peptides endogenously bound to B*0802 and 12 individual peptides purified from that mixture. The HLA-B*0802 allotype, while able to bind some peptides bound by B*0801, has a broader repertoire of endogenously bound peptides than B*0801: the peptides bound by B*0802 are more variable in length and exhibit greater diversity in the carboxyl-terminal amino acid which interacts with the F pocket.

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Authors and Affiliations

  1. Departments of Structural Biology and Microbiology & Immunology, Stanford University, Stanford, CA 94305, USA, , , , , , US
    Kelly L. Arnett, W. Huang, Nicholas M. Valiante, Linda D. Barber & P. Parham

Authors

  1. Kelly L. Arnett
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  2. W. Huang
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  3. Nicholas M. Valiante
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  4. Linda D. Barber
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  5. P. Parham
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Received: 29 October 1997

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Arnett, K., Huang, W., Valiante, N. et al. The Bw4/Bw6 difference between HLA-B*0802 and HLA-B*0801 changes the peptides endogenously bound and the stimulation of alloreactive T cells.Immunogenetics 48, 56–61 (1998). https://doi.org/10.1007/s002510050400

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