Domain interactions of H–2 class I antigens alter cytotoxic T-cell recognition sites

Abstract

H–2 class I antigens appear to direct the recognition of virus-infected and neoplastic transformed cells by cytotoxic T lymphocytes (CTLs)^1,2. Here, to identify the regions of class I antigens involved in CTL recognition, four hybrid class I genes were constructed in which exons were exchanged between the H–2K^band H–2D^b genes^3,4. These class I genes were expressed in mouse L cells and recognition of the hybrid K^b/D^bantigens by CTLs and monoclonal antibodies specific for either K^b or D^b was investigated⁴. The pattern of CTL and monoclonal antibody recognition obtained indicates three correlations between structure and function of class I antigens. First, most CTL recognition sites and alloantigenic determinants are located on domains 1 and 2 of the antigen molecule. Second, these CTL recognition sites and alloantigenic determinants are not influenced by interaction of domains 1 and 2 with polymorphic regions of domain 3. Third, in contrast, interaction between domains 1 and 2 alters these CTL recognition sites and alloantigenic determinants. The alteration of CTL recognition sites by interaction between domains 1 and 2 suggests that a CTL site may be formed by amino acids from both domains 1 and 2, or that the conformation of amino acids at a CTL site may be altered by interactions between domains 1 and 2. Through these two features, the conformation of CTL recognition sites on H–2 class I antigens may be sensitive to alteration by interaction of either domain 1 or 2 with viral antigens.