DUAL ANTIGENIC RECOGNITION BY CLONED HUMAN GAMMA-DELTA T-CELLS

The function of gamma-delta T cells is still elusive. The nature of the antigens that they recognize and the mode of presentation of these antigens are largely unknown. The majority of human peripheral gamma-delta T cells bear a V-gamma-9/V-delta-2 T cell receptor, and display nonclonal reactivity to mycobacteria, without restriction by MHC. It is unknown whether these cells have clonal antigenic specificity as well. Here we describe rheumatoid arthritis-derived V-gamma-9/V-delta-2 T cell clones, displaying dual antigenic recognition: a nonclonal, MHC-unrestricted recognition of mycobacteria, and a clonal recognition of a short tetanus toxin peptide presented by HLA-DRw53, a nonpolymorphic class II MHC molecule associated with susceptibility to rheumatoid arthritis. This is the first evidence that V-gamma-9/V-delta-2 T cells can recognize nominal antigenic peptides presented by class II MHC molecules. These results suggest that much like alpha-beta T cells, V-gamma-9/V-delta-2 cells may contribute to the immune response against foreign antigens in an antigen-specific and MHC-restricted manner. The reactivity of these gamma-delta T cells to mycobacteria may represent a superantigen-like phenomenon.