THE MURINE IMMUNE-RESPONSE TO THE MALE-SPECIFIC ANTIGEN MOUSE TESTICULAR CYTOCHROME-C

Male and female A/J mice were examined for their ability to elicit T l ymphocyte and antibody (Ab) responses to the male-specific Ag, mouse t esticular cytochrome c (Mt cyt). T lymphocytes from both male and fema le mice primed in vivo responded to the Ag in in vitro proliferation a ssays, and the dose-response curves were statistically indistinguishab le. In addition, similar levels of Ab to Mt cyt were observed in immun ized male and female mice.The B cells producing the Ab had switched is otypes to IgG1 and IgG2a, indicating that the self-reactive T helper ( Th) cells in male mice were functional.Thus, male mice do not appear t o be immunologically tolerant to Mt cyt, at least at the Th and B lymp hocyte levels. No evidence for disease was found in male mice primed w ith Mt cyt. Major histocompatibility complex (MHC) class II-positive a ntigen-presenting cells are present in the testes and these were shown in vitro to process and present Mt cyt to a T cell hybridoma specific for the synthetic peptide Mt cyt 93-104. However, the hybridoma was n ot activated in the absence of exogenous Mt cyt 93-104 or Mt cyt, indi cating that endogenous Mt cyt is not normally processed in sufficient quantity to effectively load MHC class II molecules with this particul ar Mt cyt-derived peptide. Notwithstanding any immunologic privilege o f the testes, the lack of tolerance to Mt cyt and its failure to elici t an autoimmune disease could extend from the low levels of processed Mt cyt Ag available for T cell recognition. The T cell response elicit ed by Mt cyt contrasts the lack of response to mouse somatic cytochrom e c which differs from Mt cyt at 13 amino acid residues and is express ed in most tissues and at higher levels.