T cell response pattern to glutamic acid decarboxylase 65 (GAD65) peptides of newly diagnosed type 1 diabetic patients sharing susceptible HLA haplotypes

Autoantibodies and autoreactive T lymphocytes directed against several pancreatic β cell proteins such as GAD65 have been identified in the circulation before and at the onset of clinical type 1 (insulin‐dependent) diabetes. Using GAD65 synthetic peptides, we studied the proliferative response of peripheral blood mononuclear cells (PBMC) either from recently diagnosed type 1 diabetic patients, of whom the majority share the disease‐associated HLA class II haplotype (DR4‐DQB1*0201 or DR3‐DQB1*0302), or from HLA‐matched control subjects. We found that 67% (14/21) of the type 1 diabetic patients and 39% (9/23) of the control subjects exhibited a positive proliferative response. Compared with control subjects, however, PBMC from diabetic patients proliferated more frequently (P