Molecular and Functional Bases of Self-Antigen Recognition in Long-Term Persistent Melanocyte-Specific CD8+ T Cells in One Vitiligo Patient (original) (raw)
2003, Journal of Investigative Dermatology
Vitiligo patients possess high frequencies of circulating CD8 þ T lymphocytes speci¢c for the melanocyte differentiation antigen Melan-A/MART-1. These self-spe-ci¢c T cells exhibit intact functional properties and their T cell receptors are selected for a narrow range of high a⁄nities of antigen recognition, suggesting their important role in the pathogenesis of vitiligo. In order to understand the molecular base for this unexpected, optimal T cell receptor recognition of a self-antigen, a tetramer-guided ex vivo analysis of the T cell receptor repertoire speci¢c for the Melan-A antigen in a patient a¡ected by vitiligo is reported. All T cell receptors sequenced corresponded to di¡erent clonotypes, excluding extensive clonal expansions and revealing a large repertoire of circulating Melan-A-speci¢c T lymphocytes. A certain degree of T cell receptor structural conservation was noticed, however, as a single AV segment contributed to the a chain rearrangement in 100% of clones and a conserved amino acid sequence was found in the b chain complementarity determining region 3 of various high a⁄nity cells.We suggest that the conserved a chain confers self-antigen recognition, necessary for intrathymic selection and peripheral homeostasis, to many synonymous T cell receptors, whereas the b chain ¢ne tunes the T cell receptor a⁄nity of the speci¢c cells.
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