Crystal structure of the Vd domain of a human gd T cell antigen receptor

LI, HM; LEBEDEVA M; LLERA AS; FIELDS, BA; BRENNER M; MARIUZZA, RA

NATURE

Año: 1998 vol. 391 p. 502 - 506

0028-0836

Antigen recognition by T lymphocytes is mediated by cell-surfaceglycoproteins known as T-cell antigen receptors (TCRs). These arecomposed of a and b, organd d, polypeptide chainswith variable(V) and constant (C) regions. In contrast to ab TCRs, whichrecognize antigen only as peptide fragments bound to moleculesof the major histocompatibility complex (MHC), gd TCRs appearto recognize proteins directly, without antigen processing, and torecognize MHC molecules independently of the bound peptide.Moreover, small phosphate-containing non-peptide compoundshave also been identified as ligands for certain gd T cells. Thesestudies indicate that antigen recognition by gd TCRs may befundamentally different from that by ab TCRs. The three-dimensionalstructures of several ab TCRs and TCR fragments, andtheir complexes with peptide–MHC or superantigens, havebeen determined. Here we report the crystal structure of the Vddomain of a human gd TCR at 1.9A°resolution. A comparisonwith antibody and ab TCRV domains reveals that the frameworkstructure of Vd more closely resembles that of VH than of Va, Vbor VL (where H and L refer to heavy and light chains), whereasthe relative positions and conformations of its complementaritydeterminingregions (CDRs) share features of both Va and VH.These results provide the first direct evidence that gd TCRs arestructurally distinct from ab TCRs and, together with the observationthat the CDR3 length distribution of TCR d chains issimilar to that of immunoglobulin heavy chains, are consistentwith functional studies suggesting that recognition of certainantigens by gd TCRs may resemble antigen recognition byantibodies.