Cross-restriction of a T cell clone to HLA-DR alleles associated with rheumatoid arthritis: Clues to arthritogenic peptide motifs

Autor: Nicholas Willcox, Hidenori Matsuo, Shrikant Deshpande, Michael W. Nicolle, Paul C. Driscoll, Simon Hawke, Edward G. Spack, Paul Wordsworth, Louise Corlett
Rok vydání: 1999
Předmět:
Zdroj: Arthritis & Rheumatism. 42:1040-1050
ISSN: 1529-0131
0004-3591
DOI: 10.1002/1529-0131(199905)42:5<1040::aid-anr25>3.0.co;2-x
Popis: Objective. To identify distinctive sequence motifs required for productive peptide presentation by those HLA-DR alleles/DR4 subtypes that predispose to rheumatoid arthritis (RA). Methods. We tested 10 different HLA-DR4 subtypes for presentation of acetylcholine receptor peptides to 8 different DR4-restricted T cell lines/clones in proliferation assays. Results. Seven of the 8 T cells depended absolutely on either the autologous Lys 71 (in Dw4) or Arg 71 (e.g., Dw14), despite these alleles' similar charge and RA associations. In contrast, the PM-A T cell was only mildly affected by this interchange. Moreover, after minor modifications, peptides were presented to this unusual T cell preferentially by all the RA-associated subtypes of DR4 as well as by 2 other DR alleles (DR1 and DR1402) that predispose to RA. Conclusion. This coincident cross-restriction to all the RA-associated HLA-DR alleles except DR10 shows that there could even be a single arthritogenic peptide; we now suggest a possible consensus motif.
Databáze: OpenAIRE
Externí odkaz: