Structure of a human γδ T-cell antigen receptor

T-cell antigen receptors composed of gamma and delta polypeptide chains (gamma delta TCRs) can directly recognize antigens in the form of intact proteins or non-peptide compounds, unlike alpha beta TCRs, which recognize antigens bound to major histocompatibility complex molecules (MHC). About 5% of peripheral blood T cells bear gamma delta TCRs, most of which recognize non-peptide phosphorylated antigens(1,2). Here we describe the 3.1 Angstrom resolution structure of a human gamma delta TCR from a T-cell clone(3) that is phosphoantigen-reactive. The orientation of the variable (V) and constant (C) regions of the gamma delta TCR is unique when compared with alpha beta TCRs or antibodies, and results from an unusually small angle between the V gamma and C gamma domains. The complementarity-determining regions (CDRs) of the V domains exhibit a chemically reasonable binding site for phosphorylated antigens, providing a possible explanation for the canonical usage of the V gamma9 and V delta2 gene segments by phosphoantigen-reactive receptors. Although the gamma delta TCR V domains are similar in overall structure to those of alpha beta TCRs, gamma delta TCR C domains are markedly different. Structural differences in C gamma and C delta, and in the location of the disulphide bond between them, may enable gamma delta TCRs to form different recognition/signalling complexes than alpha beta TCRs.