期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：24
页码：10978-10983
DOI：10.1073/pnas.1006545107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：A peptide derived from the insulin B chain contains a major epitope for diabetogenic CD4+ T cells in the NOD mouse model of type 1 diabetes (T1D). This peptide can fill the binding groove of the NOD MHCII molecule, IAg7, in a number of ways or "registers." We show here that a diverse set of NOD anti-insulin T cells all recognize this peptide bound in the same register. Surprisingly, this register results in the poorest binding of peptide to IAg7. The poor binding is due to an incompatibility between the p9 amino acid of the peptide and the unique IAg7 p9 pocket polymorphisms that are strongly associated with susceptibility to T1D. Our findings suggest that the association of autoimmunity with particular MHCII alleles may be do to poorer, rather than more favorable, binding of the critical self-epitopes, allowing T-cell escape from thymic deletion.
