Skin Rashes Research Today is a free monthly online journal that collates and summarizes the latest research about Skin Rashes, including details on dermatitis, itches, creams, medication, treatment.

Restricted MHC-peptide repertoire predisposes to autoimmunity.

Logunova NN, Viret C, Pobezinsky LA, Miller SA, Kazansky DB, Sundberg JP, Chervonsky AV

The Jackson Laboratory, Bar Harbor, ME 04609, USA.

MHC molecules associated with autoimmunity possess known structural features that limit the repertoire of peptides that they can present. Such limitation gives a selective advantage to TCRs that rely on interaction with the MHC itself, rather than with the peptide residues. At the same time, negative selection is impaired because of the lack of negatively selecting peptide ligands. The combination of these factors may predispose to autoimmunity. We found that mice with an MHC class II-peptide repertoire reduced to a single complex demonstrated various autoimmune reactions. Transgenic mice bearing a TCR (MM14.4) cloned from such a mouse developed severe autoimmune dermatitis. Although MM14.4 originated from a CD4+ T cell, dermatitis was mediated by CD8+ T cells. It was established that MM14.4+ is a highly promiscuous TCR with dual MHC class I/MHC class II restriction. Furthermore, mice with a limited MHC-peptide repertoire selected elevated numbers of TCRs with dual MHC class I/MHC class II restriction, a likely source of autoreactivity. Our findings may help to explain the link between MHC class I responses that are involved in major autoimmune diseases and the well-established genetic linkage of these diseases with MHC class II.

Published 6 July 2005 in J Exp Med, 202(1): 73-84.
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