Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a beta-linked self-glycolipid.
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 naïve mice show an oligoclonal TCR repertoire with predominant usage of the Valpha3/Valpha1-Jalpha7/Jalpha9 and Vbeta8.1/Vbeta3.1-Jbeta2.7 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 CDR2beta region are conserved between most type I and type II NKT TCRs, CDR 1alpha and 3alpha 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.
Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
Philomena
P
Arrenberg
Ramesh
R
Halder
Yang
Y
Dai
Igor
I
Maricic
Vipin
V
Kumar
D000595:Amino Acid Sequence; D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism; D015551:Autoimmunity; D001483:Base Sequence; D022801:Complementarity Determining Regions; D017931:DNA Primers / Q000235:genetics; D019672:Genes, T-Cell Receptor; D006017:Glycolipids / Q000737:chemistry / Q000276:immunology*; D007113:Immunity, Innate; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D055611:Natural Killer T-Cells / Q000145:classification / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015238:Sulfotransferases / Q000172:deficiency / Q000235:genetics
D055610:Antigens, CD1d; C526879:Cd1d1 protein, mouse; D022801:Complementarity Determining Regions; D017931:DNA Primers; D006017:Glycolipids; D011948:Receptors, Antigen, T-Cell; D015238:Sulfotransferases