Fine specificity analysis of lactate dehydrogenase B‐specific proliferating T cell clones: implications for the mechanism of alloreactivity

T cell clones of C57BL/6 origin which recognize porcine lactate dehydrogenase B (LDH‐BP) together with the A^b molecule were characterized in terms of fine specificity for both LDH‐B and self‐major histocompatibility complex determinants. Using antigen‐presenting cells from the A^b‐mutant strain B6.C‐H‐2^bm12 (bm12), three clonotypes could be distinguished: the first responds to LDH‐BP + bm12, the second fails to respond and the third is alloreactive to bm12. The last clone exhibits additional alloreactivities to A molecules expressed in strains of H‐2 haplotypes f, r, s, u, w6, w7, w16, w17 and w23. All three clonotypes give identical response patterns to a panel of 17 different dehydrogenase enzymes, and react to the same tryptic peptide of LDH‐BP. Thus, these clones appear to recognize the same LDH‐B epitope together with at least 3 different determinants of the A^b molecule. The data suggest that alloreactivity is more closely related to T cell specificity for self‐major histocompatibility complex than to specificity for foreign antigen.