CD8+ T cells maintain tolerance to myelin basic protein by 'epitope theft'

A Perchellet, I Stromnes, JM Pang, J Goverman - Nature immunology, 2004 - nature.com
A Perchellet, I Stromnes, JM Pang, J Goverman
Nature immunology, 2004nature.com
Myelin basic protein–specific CD8+ T cells can induce central nervous system autoimmunity;
however, immune tolerance prevents these autoreactive cells from causing disease. To
define the mechanisms that mediate tolerance, we developed two T cell receptor–transgenic
mouse lines with different affinities for the H-2Kk-restricted myelin basic protein epitope
consisting of amino acids 79–87 (MBP (79–87)). We observed both thymic deletion and
peripheral tolerance in the lower-affinity T cells. The higher-affinity T cells, however, showed …
Abstract
Myelin basic protein–specific CD8+ T cells can induce central nervous system autoimmunity; however, immune tolerance prevents these autoreactive cells from causing disease. To define the mechanisms that mediate tolerance, we developed two T cell receptor–transgenic mouse lines with different affinities for the H-2Kk-restricted myelin basic protein epitope consisting of amino acids 79–87 (MBP(79–87)). We observed both thymic deletion and peripheral tolerance in the lower-affinity T cells. The higher-affinity T cells, however, showed no evidence of tolerance induction and were able to prevent tolerance of the lower-affinity T cells by removing H-2Kk–MBP(79–87) complexes from antigen-presenting cells without proliferating. This form of immune regulation could limit responses of self-reactive T cells that escape other tolerance mechanisms.
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