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.
Reinhardt
C
C
Institute of Immunology, Ludwig-Maximilians University, Munich, Germany.
Falk
C
C
Steinle
A
A
Schendel
D J
DJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015797:HLA-B35 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D015797:HLA-B35 Antigen; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens