MHC class I allorecognition: the likes and dislikes of CTL and NK cells

An allogeneic culture was established using cells of two HLA disparate individuals. No pattern of specificity could be discerned when the 6 day culture that contained a mixture of CD4+, CD8+ and CD56+ lymphocytes was tested for cytotoxicity against a panel of target cells. Three approaches were utilized to dissect this alloresponse. A CD8+ population was selected and expanded as a line. This CTL population had predominant specificity for HLA-B35 and showed differential recognition of molecularly defined B35 subtypes. A set of CD8+ T cell clones was selected that recognized B35 transfectant cells. These clones were shown to discriminate among B35 molecular subtypes and to be peptide dependent, presumably recognizing a variety of endogenous peptides expressed in human cells. A second component of the response seemed to be mediated by activated CD56+ lymphocytes. Here strong cytotoxicity was found to be directed against MHC class I mutant cell lines, such as 721.221 and C1R, as well as against some allogeneic target cells. Transfection of Cw7 DNA into the mutant cell lines led to resistance to lysis. A hierarchy in susceptibility was found to correlate with HLA-C type in the unrelated panel: cells expressing HLA-Cw7 were found to be most resistant to lysis by this effector cell population.