296 Current Topics in Microbiology and Immunology Editors R. W. Compans, Atlanta/Georgia M. D. Cooper, Birmingham/Alabama T. Honjo, Kyoto · H. Koprowski, Philadelphia/Pennsylvania F. Melchers, Basel · M. B. A. Oldstone, La Jolla/California S. Olsnes, Oslo · M. Potter, Bethesda/Maryland P. K. Vogt, La Jolla/California · H. Wagner, Munich M.B.A. Oldstone (Ed.) Molecular Mimicry: Infection-Inducing Autoimmune Disease With 28 Figures and 9 Tables 123 Michael B.A. Oldstone, M.D. The Scripps Research Institute Department of Neuropharmacology 10550 N. Torrey Pines Road La Jolla, CA 92037 USA e-mail:
[email protected] Cover illustration by Melissa Nicholson and Kai W. Wucherpfenning The cover shows the crystal structure of the first human autoimmune T cell receptor bound to its self-peptide/MHC target. The T cell receptor originated from a patient with relapsing-remitting multiple sclerosis and is specific for a myelin basic protein peptide bound to HLA-DR2 (DRA, DRB1*1501). This structure showed a highly unusual binding topology in which the T cell receptor only contacted the N-terminal part of the self-peptide. This binding mode reduces the interaction surface with the MHC bound peptide, and places physical limits on the peptide specificity of this T cell receptor. This structure thus provides an explanation for the finding that this myelin basic protein specific T cell clone can be activated by a number of different microbial peptides that have limited sequence similarity with the self-peptide. The MHC molecule is colored blue, and the TCR alpha and beta chains yellow and red, respectively. The peptide is shown as a stick and ball model. Library of Congress Catalog Number 72-152360 ISSN 0070-217X ISBN-10 3-540-25597-4 Springer Berlin Heidelberg New York ISBN-13 978-3-540-25597-0 Springer Berlin Heidelberg New York This work is subject to copyright. All rights reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September, 9, 1965, in its current version, and permission for use must always be