This project is aimed at learning about the T cell receptors (TCR) expressed by T cells that mediate a group of inflammatory eye diseases referred to as """"""""uveitis"""""""". Most emphasis in FY 1990 has been on the isolation and characterization of the genes that code for these surface proteins used by T cells for antigen recognition. We have investigated the TCRs expressed on T cell lines and clones specific for S-antigen and interphotoreceptor retinoid-binding protein (IRBP) and compared V-region gene usage between T cells capable of transferring EAU (uveitogenic) and non-pathogenic T cells. Our analysis of the Vbeta8 gene locus for genomic rearrangements demonstrated the predominant Vbeta8 gene rearrangement, even in our most pathogenic T cell lines, suggesting that small proportions of the cells in our T cell lines that induce EAU use the Vbeta8 gene element. On the other hand, our detection of Vbeta8 transcripts in uveitogenic T cell lines and the level of Vbeta8 gene expression could be correlated with the abilities of our various T cell lines and clones to induce EAU, which suggests that T cells expressing the Vbeta8 phenotype may be involved in the etiology of EAU. However, Northern analysis using a probe specific to Vbeta8.2 revealed that, unlike the pathogenic T cells involved in other experimental autoimmune diseases, uveitogenic T cell lines express a member of the Vbeta8 TCR family that appears to be similar to but distinct from Vbeta8.2. We have cloned and sequenced the Vbeta8.2-like cDNAs derived from S-antigen and IRBP-specific uveitogenic T cell lines. The gene from the IRBP line shows approximately 99% sequence homology within rat Vbeta8.2, while the gene from the S-antigen line is only 90% homologous to Vbeta8.2.
