Antigen recognition by gammadelta T cells.
gammadelta T cells contribute to host immune competence uniquely. This is most likely because they have distinctive antigen-recognition properties. While the basic organization of gammadelta T-cell receptor (TCR) loci is similar to that of alphabeta TCR loci, there is a striking difference in how the diversity of gammadelta TCRs is generated. gammadelta and alphabeta T cells have different antigen-recognition requirements and almost certainly recognize a different set of antigens. While it is unclear what most gammadelta T cells recognize, the non-classical major histocompatibility complex class I molecules T10 and T22 were found to be the natural ligands for a sizable population (0.2-2%) of murine gammadelta T cells. The recognition of T10/T22 may be a way by which gammadelta T cells regulate cells of the immune system, and this system has been used to determine the antigen-recognition determinants of gammadelta T cells. T10/T22-specific gammadelta T cells have TCRs that are diverse in both V gene usage and CDR3 sequences. Their Vgamma usage reflects their tissue origin, and their antigen specificity is conferred by a motif in the TCR delta chain that is encoded by V and D segments and by P-nucleotide addition. Sequence variations around this motif modulate affinities between TCRs and T10/T22. That this CDR3 motif is important in antigen recognition is confirmed by the crystal structure of a gammadelta TCR bound to its ligand. The significance of these observations is discussed in the context of gammadelta T-cell biology.
Chien
Yueh-hsiu
YH
Department of Microbiology and Immunology, Program in Immunology, Stanford University, Stanford, CA, USA. chien@stanford.edu
Konigshofer
Yves
Y
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology; D001483:Base Sequence; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000276:immunology; D006649:Histocompatibility Antigens / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D020836:Protein Structure, Quaternary; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000941:Antigens; D022801:Complementarity Determining Regions; D006649:Histocompatibility Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta