• Immune responses to normal retinal proteins, including S-antigen, have been demonstrated in patients with a variety of retinal disorders, as well as in those who have received panretinal laser photocoagulation. T-cell lymphocytes (T cells) have been implicated in the pathogenesis of several ocular inflammatory diseases of possible autoimmune etiology. We used synthetic peptides that correspond to the amino acid sequence of S-antigen in lymphocyte proliferation assays to identify specific sites in the molecule recognized by human T cells. Ten patients with type II diabetes were studied before and after initial panretinal laser photocoagulation for proliferative diabetic retinopathy. T-cell responses, expressed as a stimulation index, to S-antigen and peptides were negative in all patients before treatment. Three weeks after panretinal laser photocoagulation, eight of 10 assays were positive (stimulation index >2; P<.01) when lymphocytes were stimulated with peptide BSA(273-292); six of nine were positive (P<.01) with peptide BSA(303-332); and six of six were positive (P<.001) with peptide BSA(343-362). Our study identifies several specific sites in S-antigen that elicit human immune responses. The implications of these findings with regard to the pathogenesis and treatment of autoimmune uveitis are discussed.