DIFFERENCES IN PEPTIDE PRESENTATION BETWEEN B27 SUBTYPES - THE IMPORTANCE OF THE P1 SIDE-CHAIN IN MAINTAINING HIGH-AFFINITY PEPTIDE BINDING TO B-ASTERISK-2703

被引:51
作者
COLBERT, RA [1 ]
ROWLANDJONES, SL [1 ]
MCMICHAEL, AJ [1 ]
FRELINGER, JA [1 ]
机构
[1] UNIV OXFORD, INST MOLEC MED, OXFORD OX3 9DU, ENGLAND
关键词
D O I
10.1016/1074-7613(94)90105-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Susceptibility to spondyloarthropathies is strongly associated with the MHC class I molecule HLA-B27, and is hypothesized to result from the presentation of arthritogenic peptides. Subtypes of B27 that differ structurally but are disease-associated ought to be capable of presenting such peptides, while nondisease-associated subtypes would not. We demonstrate that B*2703, the predominant West African B27 subtype that may not predispose to disease, is not recognized by most B*2705-alloreactive CTL, and does not efficiently present a known B*2705-restricted influenza A nucleoprotein (NP) peptide. We show inefficient presentation is due to a reduced binding affinity of B*2703 for the NP peptide. Furthermore, substituting Arg for the naturally occurring Ser at P1 of the NP peptide, restores high affinity binding and efficient presentation by B*2703. Our results suggest that B*2703 will bind and present efficiently only a subset of the peptides that bind to B*2705, in particular those with Arg or Lys at P1. The apparent lack of disease in individuals with B*2703 may be due to an inability to bind and present putative arthritogenic peptides.
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页码:121 / 130
页数:10
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