Degenerate recognition of a dissimilar antigenic peptide by myelin basic protein-reactive T cells. Implications for thymic education and autoimmunity.
The key event in the induction of an immune response is the recognition by a T lymphocyte of an antigenic peptide bound to a MHC molecule. In the absence of structural coordinates of the TCR and class II MHC molecules, various models of T cell recognition have been proposed, with the emerging dogma that T cell recognition is exquisitely specific. We show here that T cell clones specific for the N-terminal fragment of myelin basic protein, acetylated Ac1-11, recognize a set of unrelated peptides in the context of the same I-Au molecule. Moreover, immunization with the peptide mimic is sufficiently cross-reactive with Ac1-9 to either induce the Ac1-9-reactive clones or to induce tolerance as well as protection against Ac1-9-induced EAE. This observed degeneracy in T cell recognition has important implications for thymic selection and induction of autoimmune disease states by "molecular mimicry."
Bhardwaj
V
V
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024.
Kumar
V
V
Geysen
H M
HM
Sercarz
E E
EE
D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity; D002999:Clone Cells; D007108:Immune Tolerance; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000502:physiology*
D004676:Myelin Basic Protein; D010446:Peptide Fragments