Gamma delta T cell receptors confer autonomous responsiveness to the insulin-peptide B:9-23.

The range and physical qualities of molecules that act as ligands for the gammadelta T cell receptors (TCRs) remain uncertain. Processed insulin is recognized by alphabeta T cells, which mediate diabetes in non-obese diabetic (NOD) mice. Here, we present evidence that gammadelta T cells in these mice recognize processed insulin as well. Hybridomas generated from NOD spleen and pancreatic lymph nodes included clones expressing gammadelta TCRs that responded specifically to purified islets of Langerhans and to an insulin peptide, but not to intact insulin. The gammadelta TCRs associated with this type of response are diverse, but a cloned gammadelta TCR was sufficient to transfer the response. The response to the insulin peptide was autonomous as demonstrated by stimulating single responder cells in isolation. This study reveals a novel specificity for gammadelta TCRs, and raises the possibility that gammadelta T cells become involved in islet-specific autoimmunity.