Differences in peptide presentation between B27 subtypes: The importance of the P1 side chain in maintaining high affinity peptide binding to B{black star}2703

Robert A. Colbert, Sarah L. Rowland-Jones, Andrew J. McMichael, Jeffrey A. Frelinger

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Susceptibility to spondyloarthropathies is strongly associated with the MHC class I molecule HLA-027, 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{black star}2703, the predominant West African B27 subtype that may not predispose to disease, is not recognized by most B{black star}2705-alloreactive CTL, and does not efficiently present a known B{black star}2705-restricted influenza A nucleoproteln (NP) peptide. We show Inefficient presentation is due to a reduced binding affinity of B{black star}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{black star}2703. Our results suggest that B{black star}2703 will bind and present efficiently only a subset of the peptides that bind to B{black star}2705, in particular those with Arg or Lys at P1. The apparent lack of disease In Individuals with B{black star}2703 may be due to an inability to bind and present putative arthritogenic peptides.

Original languageEnglish (US)
Pages (from-to)121-130
Number of pages10
JournalImmunity
Volume1
Issue number2
DOIs
StatePublished - May 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Differences in peptide presentation between B27 subtypes: The importance of the P1 side chain in maintaining high affinity peptide binding to B<sup>{black star}</sup>2703'. Together they form a unique fingerprint.

  • Cite this