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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 Lys71 (in Dw4) or Arg71 (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.

Original publication

DOI

10.1002/1529-0131(199905)42:5<1040::aid-anr25>3.0.co;2-x

Type

Journal article

Journal

Arthritis and rheumatism

Publication Date

05/1999

Volume

42

Pages

1040 - 1050

Addresses

Imperial College Medical School, Charing Cross Hospital, London, UK.

Keywords

Antigen-Presenting Cells, T-Lymphocytes, Clone Cells, Humans, Arthritis, Rheumatoid, Arginine, Lysine, Tryptophan, Glycine, HLA-DR Antigens, Cross Reactions, Protein Conformation, Point Mutation, Alleles