Species-specific structural differences in the alpha 1 + alpha 2 domains determine the frequency of murine cytotoxic T cell precursors stimulated by human and murine class I molecules.
The frequency of murine CTL precursors (CTLp) that recognize the human histocompatibility Ag HLA-A2 and HLA-B7 was measured and found to be approximately two orders of magnitude lower than the frequency of CTLp that recognize murine H-2 alloantigens. The possible contribution of other cell surface molecules to this difference in response was addressed by expression of the H-2Ld molecule on a human cell and the HLA-B7 molecule on a murine cell. It was found that both human and murine H-2Ld expressing cells elicited comparable levels of H-2Ld specific CTL. Although murine HLA-B7 positive cells stimulated a higher frequency of HLA-B7-specific CTLp than did human cells, this appeared to be largely due to stimulation of CTLp that recognized HLA-B7 in the context of H-2 molecules; consequently, it was concluded that the difference in the frequency of murine CTLp elicited by human and murine class I Ag is due to species specific structural differences in these molecules. The regions of the class I molecule that were responsible for this difference were mapped using chimeric class I molecules constructed to replace domains of the human molecule with their murine counterparts. It was found that the frequency of CTLp is controlled by structures within the alpha 1 and alpha 2 domains of the molecule. These results are discussed in the light of models for T cell recognition of class I Ag and the diversification of the T cell receptor repertoire.
Engelhard
V H
VH
Department of Microbiology, University of Virginia School of Medicine, Charlottesville 22908.
Le
A X
AX
Holterman
M J
MJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002678:Chimera; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D051379:Mice; D009710:Nucleotide Mapping; D013045:Species Specificity; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology
D006183:H-2 Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I