Abundance of H‐2 promiscuous T cells specific for mycobacterial determinants in H‐2^b/d F1 hybrid mice

A majority of immunodominant epitopes of mycobacterial antigens are known to be recognized by murine T cells in the context of several H‐2 haplotypes. In this study, we established the frequency of T cells able to recognize these peptides promiscuously, i.e. in the context of allogeneic antigen‐presenting cells, using hybridomas from peptide‐immunized H‐2 homologous and heterologous mice. The degree of promiscuity in homozygous mice varied between 4–27% between different specificities and genetic backgrounds. In particular, the results showed that promiscuity between A^b and A^d in respect to a peptide from the Mycobacterium tuberculosis 38‐kDa protein (residues 350–369) was displayed by 22% of BALB/c and 4% of C57BL/10‐derived hybrids, but by 42% of [BALB/c x C57BL/10] F1‐derived clones. This represents a significant increase (p < 0.001) of T cell promiscuity compared to the parental haplotypes. It is noteworthy that considerably lower peptide concentrations were able to stimulate the promiscuous hybridomas compared to the H‐2‐restricted hybrids. This finding suggests a functional advantage of promiscuous T cells which enables them to expand preferentially in the initial stages of infections with M. tuberculosis and thus enables the host to mount a rapid protective immune response.