Abstract
Townsend and colleagues (1) were the first to demonstrate, in 1984, that target cells that had been transfected with single viral RNA segments could be specifically recognized by cytotoxic T lymphocytes (CTL). Recombinant vaccinia viruses that expressed single-gene products were subsequently used to identify major target antigens for CTL (2,3). The demonstration that CTL could recognize transfectants that expressed only fragments of a given target antigen (4) led to the use of overlapping fragments and synthetic peptides to localize epitopes. It was subsequently established that target cells that had been incubated with short synthetic peptides corresponding to the sequence of the influenza virus nucleoprotein (NP) could be specifically recognized by NP-specific CTL in a major histocompatability complex (MHC) class I restricted manner (5,6). Bjorkman et al. (6,7) subsequently resolved the structure of the human class I molecule HLA-A2 by x-ray crystallography and provided evidence of a putative peptide binding site. These studies provided the foundation for characterizing CTL epitopes and CTL responses in many disease systems. Numerous CTL epitopes have been now identified, in all cases recognized in the context of a single human lymphocyte antigen (HLA) allele or family of closely related (HLA degenerate) alleles, and the use of synthetic peptides for defining the types of immune responses induced by experimental vaccination or natural exposure to the target pathogen has been now well documented.
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References
Townsend, A. R. M., McMichael, A. J, Carter, N. P., Huddleston, J. A., and Brownlee, G. G. (1984) Cytotoxic T cell recognition of the influenza virus nucleoprotein and hemagglutinin expressed in transfected mouse L cells. Cell 39, 13ā25.
Gotch, F. M., McMichael, A. J., Smith, G. L., and Moss, B. (1986) Identification of the viral molecules recognized by influenza specific human cytotoxic T lymphocytes. J. Exp. Med. 165, 408ā416.
Yewdell, J. W., Bennink, J. R., Smith, G. L., and Moss, B. (1985) Influenza A virus nucleoprotein is a major target antigen for cross reactive anti-influenza A virus cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. USA 82, 1785ā1789.
Townsend, A. R. M., Gotch, F. M., and Davey, J. (1985) Cytotoxic T cells recognize fragments of influenza nucleoprotein. Cell 42, 457ā467.
Townsend, A. R. M., Rothbard, J., Gotch, F. M., Bahadur, G., Wraith, D., and McMichael, A. J. (1986) The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44, 959ā968.
Gotch, F., Rothbard, J., Howl, K., Townsend, A., and McMichael, A. (1987) Cytotoxic T lymphocytes recognize a fragment of influenza virus matrix protein in association with HLA-A2. Nature (London) 326, 881,882.
Gotch, F. M., McMichael, A. J., Smith, G. L., and Moss, B. (1986) J. Exp. Med. 165, 408ā416.
Bjorkman, P. J., Saper, M. A., Samraoui, B., Bennett, W. S., Strominger, J. L., and Wiley, D. C. (1987a) Structure of the human class I histoincompatibility antigen, HLA-A2. Nature 329, 506ā512.
Bjorkman, P. J., Saper, M. A., Samraoui, B., Bennett, W. S., Strominger, J. L., and Wiley, D. C. (1987b) The foreign antigen-binding site T cell recognition regions of class I histoincompatibility antigens. Nature 329, 512ā518.
Hogan, K. T., Shimojo, N., Walk, S. F., Engelhard, V. H., Maloy, W. L., Coligan, J. E., et al. (1988) Mutations in the Ī±-helix of HLA-A2 affect presentation but do not inhibit binding of influenza virus matrix peptide. J. Exp. Med. 168, 725ā736.
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Doolan, D.L. (2002). Assessing Antigen-Specific CD8+ CTL Responses in Humans. In: Doolan, D.L. (eds) Malaria Methods and Protocols. Methods in Molecular Medicineā¢, vol 72. Humana Press. https://doi.org/10.1385/1-59259-271-6:445
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DOI: https://doi.org/10.1385/1-59259-271-6:445
Publisher Name: Humana Press
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