Influenza A-specific, HLA-A2.1-restricted cytotoxic T lymphocytes from HLA-A2.1 transgenic mice recognize fragments of the M1 protein.
Previous studies have indicated that in transgenic mice expressing human class I MHC molecules, it is difficult to demonstrate a significant CTL response to a viral Ag in the context of the transgenic molecule. In this paper, a procedure is reported for the isolation of influenza-specific murine CTL restricted by the human class I molecule HLA-A2.1. The principal specificity of such CTL is for a fragment of the influenza M1 protein that has been previously shown to be immunodominant for human HLA-A2.1-restricted CTL. CTL of this specificity were also established through the use of peptide-pulsed rather than virus-infected stimulators. The dependence of murine CTL recognition upon peptide length and HLA-A2 structure was established to be similar to that previously reported for human CTL. However, the fine specificity of CTL maintained on virus-infected stimulators was somewhat different from that of CTL maintained with M1 peptide. This suggests that differences in surface density or peptide structure between peptide-pulsed and virus-infected stimulators may result in the outgrowth of T cells with different receptor structures. The immunodominance of the M1 peptide determinant in both mice and humans suggests that species-specific differences in TCR structure, Ag-processing systems, and self-tolerance are of less importance than limitations on the ability of antigenic peptides to bind to appropriate class I molecules. These results thus establish the utility of the transgenic system for the identification of human class I MHC-restricted T cell epitopes.
Engelhard
V H
VH
Department of Microbiology, University of Virginia, Charlottesville 22908.
Lacy
E
E
Ridge
J P
JP
D000596:Amino Acids / Q000276:immunology; D000818:Animals; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*
D000596:Amino Acids; D000939:Epitopes; D015789:HLA-A2 Antigen; C031540:M-protein, influenza virus; C488936:M1 protein, Influenza A virus; D014763:Viral Matrix Proteins