T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes

International Immunology
S BayrakN A Mitchison

Abstract

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the ...Continue Reading

Citations

Dec 4, 1998·Springer Seminars in Immunopathology·B MüllerZ Yin
Dec 16, 2010·The Journal of Clinical Investigation·Yawei LiuShohreh Issazadeh-Navikas
Nov 11, 2008·Arthritis Research & Therapy·Keiichi IwanamiTakayuki Sumida
Nov 11, 2009·Arthritis Research & Therapy·Keiichi IwanamiTakayuki Sumida
Dec 9, 1998·Clinical and Experimental Immunology·R O Williams
Aug 25, 2000·Autoimmunity·M Hesse, N A Mitchison
May 20, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Linda K MyersAndrew H Kang

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