T cell response to myoglobin: a comparison of T cell clones in high‐responder and low‐responder mice

Mice carrying the H‐2^b haplotype (e.g., inbred strains C57BL/6 and C57BL/10) are low responders to sperm whale myoglobin when tested in the T cell proliferation assay. Their response is improved by the removal of the Ly‐2 cells from the lymph node population, but it still remains significantly lower than that of cells from high‐responder strains (e.g., DBA/2, H‐2^d). To determine whether T cells from the low and high‐responder mice recognize the same or different epitopes on the immunizing antigen, we obtained sets of T cell clones from both strains and tested them against peptides representing different regions of the myoglobin molecule, as well as against myoglobins from species other than the sperm whale. Four types of T cell clones were obtained from the DBA/2 mice: 3 types responded to the peptide 107–120 (9 clones altogether), and 1 type responded to the peptide 133–149 (4 clones altogether). The 3 types responding to the peptide 107–120 could be distinguished by their response to horse myoglobin or by the restriction of the response (A^d vs. E^d). Similarly, 5 types of T cell clones were obtained from the C57BL/6 mice: 2 types responded to the peptide 10–22 (1 type, but not the other, responded to horse myoglobin); 1 type responded to the peptide 133–149; and 2 types did not respond to any of the peptides used (1 type, but not the other, responded to dog myoglobin). All 5 types (13 clones altogether) were presumably A^b restricted. These results demonstrate the diversity of epitopes in single antigenic regions and show equivalent heterogeneity of T cell repertoires in high and low responder mice. Attempts to demonstrate specific T cell suppression in the low responder mice failed; only partial, nonspecific suppression was observed.