CD8+ T cells maintain tolerance to myelin basic protein by 'epitope theft'.
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-2K(k)-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-2K(k)-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.
Perchellet
Antoine
A
Department of Immunology, University of Washington, Box 357650, Seattle, Washington 98195, USA.
Stromnes
Ingunn
I
Pang
Jennifer M
JM
Goverman
Joan
J
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
D000939:Epitopes; D004676:Myelin Basic Protein; D010455:Peptides; D011948:Receptors, Antigen, T-Cell