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. We had previously shown that T cells expressing Vbeta8 gene elements are enriched in uveitogenic but not in nonpathogenic T cell lines with the same antigen fine specificity and may play a role in experimental autoimmune uveoretinitis (EAU). Most emphasis in FY 1991 has been on analyzing the TCR Vbeta8 repertoire induced by two immunodominant and uveitogenic determinants derived from interphotoreceptor retinoid-binding protein (IRBP) and S-antigen. Our results show that (1) the TCR Vbeta8 repertoire induced by immunization with S-antigen is different from that induced by IRBP: While Vbeta8 gene expression in S-antigen-specific T cell lines is restricted to Vbeta8.2 TCR, IRBP-specific lines express, in addition to Vbeta8.2, another member of the of the Vbeta8 family TCR, namely Vbeta8.3. Furthermore, the Vbeta8.2 and Vbeta8.3 subfamilies in line cells sensitized against IRBP were found to be heterogeneous, with variants differing by a few amino acid substitutions. These isoforms were designated Vbeta8.2b, Vbeta8.2c, and Vbeta8.3b. (2) Unlike experimental allergic encephalomyelitis (EAE) in which predominant usage of Vbeta8.2 gene element is observed among encephalitogenic T cells, EAU-inducing T cell lines do not predominantly utilize this Vbeta8 gene element. However, predominant usage of Vbeta8.3 gene element by one of our IRBP-specific uveitogenic T cell lines was demonstrated by genomic Southern analysis. (3) In contrast to findings among lymphocytes that are specific against xenographic antigens (eg, cytochrome c and sperm whale myoglobin), showing that TCR specific to the same antigen fine specificity utilize very similar junctional secquences; uveitogenic T cell with the same antigen fine specificity express different junctional sequences. Furthermore, a subpopulation of T cells present in both IRBP and S-antigen-specific T cell lines was found to express TCR with similar junctional sequences.
