Human cytotoxic T-lymphocyte recognition of an HLA-A3 gene product expressed on murine L cells: the only human gene product required on the target cells for lysis is the class I heavy chain.
To dissect the molecular basis for T-cell recognition of class I major histocompatibility complex antigens, we have examined the ability of human cytotoxic T lymphocytes (CTL) to recognize murine L cells transformed with a human class I gene. Three transformed L-cell lines were generated that expressed the human HLA-A3 gene from donor E1 at levels comparable to those of the endogenous L-cell H-2Kk molecules. CTL were generated in secondary and tertiary mixed lymphocyte culture against the HLA-A3 subtype of donor E1 by culturing irradiated E1 peripheral blood lymphocytes with the peripheral blood lymphocytes of responder donor M3 (M3 shares all defined class I antigens with E1 but expresses a different HLA-A3 subtype). Each of the HLA-A3-transformed L cells was lysed by M3 anti-E1 CTL in a short-term 51Cr release assay and this recognition was blocked by a monoclonal anti-HLA-A3 antibody. Antibodies specific for the human T8 and LFA-1 molecules on the CTL effectors (but absent from the transformed targets) also blocked lysis of each of the HLA-A3 transformed L-cell targets. Antibodies to other T-cell molecules failed to block lysis. The present results demonstrate that human CTL can recognize human class I molecules on targets that do not express any other human gene product and further suggest that effector T-cell molecules T8 and LFA-1 are functionally involved in this recognition process.
D000818:Animals; D000911:Antibodies, Monoclonal; D001221:Aspartate Carbamoyltransferase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); D004080:Dihydroorotase; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000235:genetics*; D015791:HLA-A3 Antigen; D006801:Humans; D051379:Mice; D009097:Multienzyme Complexes; D011506:Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014170:Transformation, Genetic
D000911:Antibodies, Monoclonal; C033626:CAD trifunctional enzyme; D006680:HLA Antigens; D015791:HLA-A3 Antigen; D009097:Multienzyme Complexes; D011506:Proteins; D001221:Aspartate Carbamoyltransferase; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)