The α-3 domain of class I MHC proteins influences cytotoxic T lymphocyte recognition of antigenic determinants located within the α-1 and α-2 domains

An interspecies class I MHC molecule, K^b1+2/A2 (in which the α-1 and α-2 domains of the H-2K^b molecule have been linked to the α-3, transmembrane and intracytoplasmic domains of the HLA-A2 molecule) has been expressed on both human and mouse target cells by gene transfer. Maintenance of serologic determinants has been demonstrated. However, decreased lysis by allospecific CTL populations of cell lines that expressed a hybrid interspecies class I molecule, K^b1+2/A2, as compared with lines that expressed the native Ag, H-2K^b, has been described. An analysis with a limited panel of H-2k^b allospecific clones demonstrated that not all H-2K^b-specific CTL can lyse cells that express K^b1+2/A2 Ag. This suggested that the reduction of lysis by CTL populations was due to the loss of specific alloreactive clones in the population. Each clone used in this study was then defined as having high or low affinity characteristics. No correlation between the affinity of the CTL and the ability to recognize the interspecies hybrid molecule could be shown. Rather, these data suggest that antigenic determinants that are located within the polymorphic domains, α-1 and α-2, may be conformationally influenced by the α-3 domain.