Role of self-Ia antigen in the recognition of self and not self by T cells: Study by use of cloned T cell lines.

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1. Even by use of I-A^KK gene-transfected L cells as antigen presenting cells (APC), azobenzenearso- nate-tyrosine (ABA-tyr) specific T cell clones or T hybridomas (I-A^kk restricted) showed increase in DNA synthesis or IL 2 production in respones to ABA-tyr, and these responses were blocked by anti-I-A^KK antibody. 2. To study directly antigen recognition of T cells, we examined changes in Ca^<2+>2 influx and membrane fluidity of T cells after antigen recognition by stopped flow method using fluorescent probes. In the presence of I-A^KK gene-transfected L cells or liposomes conjugated with Ia^KK molecules, ABA-tyr specific T cells showed marked increase in Ca^<2+>2 influx and membrane fluidity within 2 seconds after stimulation with ABA-tyr, and these responses were blocked by anti-I-A^KK antibody. 3. To clarify whether ABA-tyr should bind to Ia molecules before being recognized by T cells, we compared the rate constants of Ca^<2+>2 influx when the order of mixing of T cells, ABA-tyr and APC was changed. The rate constant was almost the same even by change in the order of mixing. These results support the trimolecular complex model of antigen recognition by T cells. 4. Among auto-Ia-reactive T cell clones, noe clone elicited lichen planus-like lesion in the skin of syngeneic mice. Another clone injected i.v. into syngeneic mice caused production of anti-DNA antibody and auto-antibody to erythrocytes. We ate exploring the causes of autoimmune diseases by use of these auto-Ia-reactive T cell clones.