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 γδ T cell receptors (TCRs) remain uncertain. Processed insulin is recognized by αβ T cells, which mediate diabetes in non-obese diabetic (NOD) mice. Here, we present evidence that γδ T cells in these mice recognize processed insulin as well. Hybridomas generated from NOD spleen and pancreatic lymph nodes included clones expressing γδ TCRs that responded specifically to purified islets of Langerhans and to an insulin peptide, but not to intact insulin. The γδ TCRs associated with this type of response are diverse, but a cloned γδ 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 γδ TCRs, and raises the possibility that γδ T cells become involved in islet-specific autoimmunity.