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 gamma delta T cell receptors (TCRs) remain uncertain. Processed insulin is recognized by alpha beta T cells, which mediate diabetes in non-obese diabetic (NOD) mice. Here, we present evidence that gamma delta T cells in these mice recognize processed insulin as well. Hybridomas generated from NOD spleen and pancreatic lymph nodes included clones expressing gamma delta TCRs that responded specifically to purified islets of Langerhans and to an insulin peptide, but not to intact insulin. The gamma delta TCRs associated with this type of response are diverse, but a cloned gamma delta 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 gamma delta TCRs, and raises the possibility that gamma delta T cells become involved in islet-specific autoimmunity. (C) 2009 Elsevier Ltd. All rights reserved.