Influenza A-specific, HLA-A2.1-restricted cytotoxic T lymphocytes from HLA-A2.1 transgenic mice recognize fragments of the M1 protein Journal Article


Authors: Engelhard, V. H.; Lacy, E.; Ridge, J. P.
Article Title: Influenza A-specific, HLA-A2.1-restricted cytotoxic T lymphocytes from HLA-A2.1 transgenic mice recognize fragments of the M1 protein
Abstract: 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.
Keywords: domain; self-tolerance; hla; foreign antigen; cell responses; binding-site; alpha-3; i histocompatibility antigens; defined epitope differences; immunogenic peptides; matrix peptide
Journal Title: Journal of Immunology
Volume: 146
Issue: 4
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 1991-02-15
Start Page: 1226
End Page: 1232
Language: English
ACCESSION: WOS:A1991EW68100023
PROVIDER: wos
PUBMED: 1704033
Notes: Source: Wos
Citation Impact
MSK Authors
  1. Elizabeth H Lacy
    74 Lacy