The Qa2 subregion controls the expression of two antigens recognized by H-2-unrestricted cytotoxic T cells

B6.K1 mice were immunized with spleen cells from B6.K2, a Qa2-subregion congenic strain. Cytotoxic T cells were generated that recognize two target antigens controlled by this region. One of the target antigens is Qa-2. This was demonstrated by the findings that pretreatment of target cells with monoclonal anti-Qa-2 antibody blocked lysis of target cells, and Qa-2 target antigens and serological determinants had a concordant distribution on a panel of B10.W (wild) mice. The gene controlling the Qa-2 target antigen is not polymorphic because B6.K2 and three strains of Qa-2⁺ B10.W mice express the same antigens, as determined by a CTL cold target competition assay. Anti-Qa-2 CTL were H-2 unrestricted because effector cells lysed Qa-2⁺ targets irrespective of their H-2 haplotype, including five B10.W strains, and lysis was not inhibited by pretreating target cells with anti-H-2 sera. The Qa2 subregion does not act as a restricting locus for anti-minor-H antigen CTL. A second target antigen was detected that was associated with the expression of the Qa-5 determinant. However, CTL activity could not be blocked by pretreating target cells with monoclonal anti-Qa-5. Therefore, the CTL target antigen may be expressed on a Qa-5^- molecule. Although the Qa-5 associated CTL specificity is only detected on H-2D^b strains, it is unlikely that CTL recognition is H-2 restricted because anti-H-2^b sera have no effect in blocking this reactivity. Qa-2 and H-2 class I antigens share a similar structure and serve as target antigens for unrestricted CTL. However, unlike class I H-2 genes, Qa-2 neither restricts antigen-specific CTL nor is polymorphic. Therefore, it is likely that Qa-2 and H-2 are derived from a common ancestral gene and have evolved to serve different functions.