Abstract
CTL specific for the influenza A virus matrix peptide 57-68 and restricted by HLA-A2 were studied. Their ability to recognize a set of analogue peptides, each of which differed from the natural peptide by a single amino acid, was analyzed. This revealed a core of five amino acids, 61-65, where one or more changes completely abrogated recognition. The glycine at position 61 was the only residue where no substitution was tolerated. Analogue peptides that did not induce CTL- mediated lysis were tested as competitors with the natural peptide; those with substitutions at positions 60, 64, and 65 inhibited, identifying residues that interact with the TCR. Another approach was to test a set of four CTL clones on all of the analogues. Marked differences in recognition by individual CTL clones were observed for several substituted peptides. The data indicate that most of the analogues bind to HLA-A2 with possible differences in fine positioning of the peptide. An alpha helical orientation for the peptide is discussed.
Full Text
The Full Text of this article is available as a PDF (733.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bastin J., Rothbard J., Davey J., Jones I., Townsend A. Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T lymphocytes. J Exp Med. 1987 Jun 1;165(6):1508–1523. doi: 10.1084/jem.165.6.1508. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
- Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
- Dongworth D. W., McMichael A. J. Inhibition of human T lymphocyte function with monoclonal antibodies. Br Med Bull. 1984 Jul;40(3):254–261. doi: 10.1093/oxfordjournals.bmb.a071986. [DOI] [PubMed] [Google Scholar]
- Gotch F. M., Kelly C., Ellis S. A., Wallace L., Rickinson A. B., van der Poel J., Crumpton M. J., McMichael A. J. Characterization of the HLA-A2.2 subtype: T cell evidence for further heterogeneity. Immunogenetics. 1985;21(1):11–23. doi: 10.1007/BF00372237. [DOI] [PubMed] [Google Scholar]
- Gotch F., Rothbard J., Howland K., Townsend A., McMichael A. Cytotoxic T lymphocytes recognize a fragment of influenza virus matrix protein in association with HLA-A2. 1987 Apr 30-May 6Nature. 326(6116):881–882. doi: 10.1038/326881a0. [DOI] [PubMed] [Google Scholar]
- McMichael A. J., Askonas B. A. Influenza virus-specific cytotoxic T cells in man; induction and properties of the cytotoxic cell. Eur J Immunol. 1978 Oct;8(10):705–711. doi: 10.1002/eji.1830081007. [DOI] [PubMed] [Google Scholar]
- McMichael A. J., Ting A., Zweerink H. J., Askonas B. A. HLA restriction of cell-mediated lysis of influenza virus-infected human cells. Nature. 1977 Dec 8;270(5637):524–526. doi: 10.1038/270524a0. [DOI] [PubMed] [Google Scholar]
- Santos-Aguado J., Biro P. A., Fuhrmann U., Strominger J. L., Barbosa J. A. Amino acid sequences in the alpha 1 domain and not glycosylation are important in HLA-A2/beta 2-microglobulin association and cell surface expression. Mol Cell Biol. 1987 Mar;7(3):982–990. doi: 10.1128/mcb.7.3.982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sette A., Buus S., Colon S., Smith J. A., Miles C., Grey H. M. Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells. 1987 Jul 30-Aug 5Nature. 328(6129):395–399. doi: 10.1038/328395a0. [DOI] [PubMed] [Google Scholar]
- Townsend A. R., Gotch F. M., Davey J. Cytotoxic T cells recognize fragments of the influenza nucleoprotein. Cell. 1985 Sep;42(2):457–467. doi: 10.1016/0092-8674(85)90103-5. [DOI] [PubMed] [Google Scholar]
- Townsend A. R., McMichael A. J., Carter N. P., Huddleston J. A., Brownlee G. G. Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed in transfected mouse L cells. Cell. 1984 Nov;39(1):13–25. doi: 10.1016/0092-8674(84)90187-9. [DOI] [PubMed] [Google Scholar]
- Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
- Townsend A. R., Skehel J. J. The influenza A virus nucleoprotein gene controls the induction of both subtype specific and cross-reactive cytotoxic T cells. J Exp Med. 1984 Aug 1;160(2):552–563. doi: 10.1084/jem.160.2.552. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yewdell J. W., Bennink J. R., Smith G. L., Moss B. Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1785–1789. doi: 10.1073/pnas.82.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinkernagel R. M., Doherty P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974 Apr 19;248(5450):701–702. doi: 10.1038/248701a0. [DOI] [PubMed] [Google Scholar]
- Zweerink H. J., Askonas B. A., Millican D., Courtneidge S. A., Skehel J. J. Cytotoxic T cells to type A influenza virus; viral hemagglutinin induces A-strain specificity while infected cells confer cross-reactive cytotoxicity. Eur J Immunol. 1977 Sep;7(9):630–635. doi: 10.1002/eji.1830070910. [DOI] [PubMed] [Google Scholar]