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

Hawke, S; Matsuo, H; Nicolle, M; Wordsworth, P; Corlett, L; Spack, E; ... Willcox, N; + view all (1999) Cross-restriction of a T cell clone to HLA-DR alleles associated with rheumatoid arthritis: clues to arthritogenic peptide motifs. Arthritis and Rheumatism , 42 (5) 1040 - 1050.

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Abstract

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

Type:Article
Title:Cross-restriction of a T cell clone to HLA-DR alleles associated with rheumatoid arthritis: clues to arthritogenic peptide motifs
Additional information:UI - 99255041 LA - Eng RN - 0 (HLA-DR Antigens) RN - 56-40-6 (Glycine) RN - 56-87-1 (Lysine) RN - 7004-12-8 (Arginine) RN - 73-22-3 (Tryptophan) PT - JOURNAL ARTICLE DA - 19990521 IS - 0004-3591 SB - A SB - M CY - UNITED STATES JC - 90M AA - Author EM -199907
Keywords:cell, peptides, Antigens, Lysine, Arginine, Tryptophan, United States, Alleles, Antigen-Presenting Cells, Arthritis, Rheumatoid, CELLS, Clone Cells, Cross Reactions, cytology, genetics, Glycine, HLA-DR Antigens, immunology, Methods, pathology, Point Mutation, Protein Conformation, Support, Non-U.S.Gov't, T-Lymphocytes, Ras, Receptor
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of)

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