SELECTION OF HUMAN TCR-V GENE FAMILIES IN AUTOLOGOUS MIXED LYMPHOCYTEREACTIONS - RELEVANCE TO AUTOIMMUNE IMMUNOPATHOLOGY

We have postulated that in vivo autologous mixed lymphocyte reactions (AMLRs) are one mechanism in the development of the intrathyroidal lym phocytic infiltration of human autoimmune thyroid disease. Such a mech anism would explain the significant numbers of self-reactive T cells p resent in thyroid infiltrates as evidenced by cloning studies. However , infiltrating T cells in a variety of autoimmune diseases including a utoimmune thyroid disease, demonstrate bias in their use of T cell rec eptor (TcR) V gene families. In order to examine whether such TcR V ge ne bias may occur secondary to non-antigen specific in vivo AMLRs rath er than secondary to specific autoantigen driven mechanisms we have ex amined the human TcR repertoire after prolonged AMLRs in vitro. Using 5 healthy donors in 1, 2 and 3 week AMLRs we showed stimulation indice s of 3.1-6.5 after 3 weeks. The hTcR V alpha and V beta gene repertoir e was assessed using the PCR technique and revealed an almost complete repertoire of V gene families at the beginning of the studies while a t the end of 3 weeks a mean of only 5.2 V alpha genes were transcribed . Less restriction was seen in the hTcR V beta repertoire with a mean of 9 V beta genes used. These data demonstrate that the AMLR is able t o mimic the marked bias in hTcR V gene family use seen within the infl amamatory infiltrates of autoimmune diseases.