STRUCTURE OF THE V-DELTA DOMAIN OF A HUMAN GAMMA-DELTA T-CELL ANTIGENRECEPTOR

Antigen recognition by T lymphocytes is mediated by cell-surface glyco proteins known as T-cell antigen receptors (TCRs). These are composed of alpha and beta, or gamma and delta, polypeptide chains with variabl e (V) and constant (C) regions, In contrast to alpha beta TCRs, which recognize antigen only as peptide fragments bound to molecules of the major histocompatibility complex (MHC), gamma delta TCRs appear to rec ognize proteins directly, without antigen processing, and to recognize MHC molecules independently of the bound peptide(1-4). Moreover, smal l phosphate-containing non-peptide compounds have also been identified as ligands far certain gamma delta T cells(5,6). These studies indica te that antigen recognition by gamma delta TCRs may be fundamentally d ifferent from that by alpha beta TCRs. The three-dimensional structure s of several ap TCRs and TCR fragments(7-10), and their complexes with peptide-MHC or superantigens(9-11), have been determined. Here we rep ort the crystal structure of the V delta domain of a human gamma delta TCR at 1.9 Angstrom resolution. A comparison with antibody and alpha beta TCR V domains reveals that the framework structure of V delta mor e closely resembles that of VH than of V alpha; V beta or VL (where H and L refer to heavy and light chains), whereas the relative positions and conformations of its complementarity-determining regions (CDRs) s hare features of both V alpha and VH. These results provide the first direct evidence that gamma delta TCRs are structurally distinct from a lpha beta TCRs and, together with the observation that thr CDR3 length distribution of TCR delta chains is similar to that of immunoglobulin heavy chains(12), are consistent with functional studies suggesting t hat recognition of certain antigens by gamma delta TCRs may resemble a ntigen recognition by antibodies(1-3).