Arsonate-specific murine T cell clones. III. Correlation between clonotype expression and fine specificity for analogs of L-tyrosine-p-azobenzenearsonate.

Despite recent advances in our understanding of T cell antigen receptor structure, relatively little is known about the role of this receptor in MHC-restricted antigen recognition. To study this problem, we have developed a panel of ABA-Tyr-reactive, I-Ak-restricted T cell clones that differ in their ability to recognize structural analogs of ABA-Tyr. Three fine specificity groups have been defined. In each group, ABA-Tyr elicited the strongest response of any of the antigens tested. Group I clones responded to ABA-conjugated hydroxyphenyl-ethanol (ABA-HPE). Group II clones responded to ABA-conjugated hydroxyphenyl-methanol (ABA-HPM) but not to ABA-HPE, and group III clones responded only to ABA-Tyr. These studies show that differences as small as a single methylene group can dramatically affect fine specificity. Because these clones are all I-Ak-restricted, it was possible to correlate receptor serology with fine specificity. To this end, monoclonal anti-clonotypes were made against clone 16-F2 from group I and used to study the relationship between fine specificity and clonotype expression. A panel of 15 T cell clones studied with four anti-clonotype antibodies showed a strict correlation between clonotype expression and fine specificity. Taken together, these data suggest that the structure recognized by the anti-clonotype antibodies is a determinant of receptor fine specificity.