期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2010
卷号:107
期号:24
页码:10984-10989
DOI:10.1073/pnas.1000576107
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:TCR-mediated recognition of {beta}-linked self-glycolipids bound to CD1d is poorly understood. Here, we have characterized the TCR repertoire of a CD1d-restricted type II NKT cell subset reactive to sulfatide involved in the regulation of autoimmunity and antitumor immunity. The sulfatide/CD1d-tetramer+ cells isolated from naive mice show an oligoclonal TCR repertoire with predominant usage of the V{alpha}3/V{alpha}1-J{alpha}7/J{alpha}9 and V{beta}8.1/V{beta}3.1-J{beta}2.7 gene segments. The CDR3 regions of both the {alpha}- and {beta}-chains are encoded by either germline or nongermline gene segments of limited lengths containing several conserved residues. Presence of dominant clonotypes with limited TCR gene usage for both TCR {alpha}- and {beta}-chains in type II NKT cells reflects specific antigen recognition not found in the type I NKT cells but similar to the MHC-restricted T cells. Although potential CD1d-binding tyrosine residues in the CDR2{beta} region are conserved between most type I and type II NKT TCRs, CDR 1{alpha} and 3{alpha} regions differ significantly between the two subsets. Collectively, the TCR repertoire of sulfatide-reactive type II NKT cells exhibits features of both antigen-specific conventional T cells and innate-like cells, and these findings provide important clues to the recognition of {beta}-linked glycolipids by CD1d-restricted T cells in general.