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. 1989 Aug;8(8):2321–2328. doi: 10.1002/j.1460-2075.1989.tb08359.x

Identification of residues necessary for clonally specific recognition of a cytotoxic T cell determinant.

J B Rothbard 1, R M Pemberton 1, H C Bodmer 1, B A Askonas 1, W R Taylor 1
PMCID: PMC401165  PMID: 2477244

Abstract

The residues in an influenza nucleoprotein (NP) cytotoxic T cell determinant necessary for cytotoxic T cell (CTL) recognition, were identified by assaying the ability of hybrid peptides to sensitize a target cell to lysis. The hybrid peptides were formed by substituting amino acids from one determinant (influenza NP 147-158) for the corresponding residues of a second peptide (HLA CW3 171-182) capable of binding to a common class I protein (H-2Kd). Six amino acids resulted in partial recognition; however, the presence of a seventh improved the potency of the peptide. Five of the six amino acids were shown to be required for recognition. The spacing of the six amino acids was consistent with the peptide adopting a helical conformation when bound. The importance of each amino acid in CTL recognition and binding to the restriction element was investigated further by assaying the ability of peptides containing point substitutions either to sensitize target cells or to compete with the natural NP sequence for recognition by CTL. The T cell response was much more sensitive to substitution than the ability of the peptide to bind the restriction element. Collectively the separate strategies identified an approximate conformation and orientation of the peptide when part of the complex and permitted a potential location in the MHC binding site to be identified. The model provides a rationalization for analogues which have previously been shown to exhibit greater affinity for the class I molecule and suggests that the binding site in major histocompatibility complex (MHC) class I molecules might have greater steric constraints that the corresponding area of class II proteins.

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Selected References

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  1. Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Bell J. I., Denney D., Jr, Foster L., Belt T., Todd J. A., McDevitt H. O. Allelic variation in the DR subregion of the human major histocompatibility complex. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6234–6238. doi: 10.1073/pnas.84.17.6234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Bodmer H. C., Pemberton R. M., Rothbard J. B., Askonas B. A. Enhanced recognition of a modified peptide antigen by cytotoxic T cells specific for influenza nucleoprotein. Cell. 1988 Jan 29;52(2):253–258. doi: 10.1016/0092-8674(88)90514-4. [DOI] [PubMed] [Google Scholar]
  7. Buus S., Sette A., Colon S. M., Jenis D. M., Grey H. M. Isolation and characterization of antigen-Ia complexes involved in T cell recognition. Cell. 1986 Dec 26;47(6):1071–1077. doi: 10.1016/0092-8674(86)90822-6. [DOI] [PubMed] [Google Scholar]
  8. Buus S., Sette A., Colon S. M., Miles C., Grey H. M. The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science. 1987 Mar 13;235(4794):1353–1358. doi: 10.1126/science.2435001. [DOI] [PubMed] [Google Scholar]
  9. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  10. Gotch F., McMichael A., Rothbard J. Recognition of influenza A matrix protein by HLA-A2-restricted cytotoxic T lymphocytes. Use of analogues to orientate the matrix peptide in the HLA-A2 binding site. J Exp Med. 1988 Dec 1;168(6):2045–2057. doi: 10.1084/jem.168.6.2045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Guillet J. G., Lai M. Z., Briner T. J., Buus S., Sette A., Grey H. M., Smith J. A., Gefter M. L. Immunological self, nonself discrimination. Science. 1987 Feb 20;235(4791):865–870. doi: 10.1126/science.2433769. [DOI] [PubMed] [Google Scholar]
  12. Guillet J. G., Lai M. Z., Briner T. J., Smith J. A., Gefter M. L. Interaction of peptide antigens and class II major histocompatibility complex antigens. Nature. 1986 Nov 20;324(6094):260–262. doi: 10.1038/324260a0. [DOI] [PubMed] [Google Scholar]
  13. Maryanski J. L., Pala P., Cerottini J. C., Corradin G. Synthetic peptides as antigens and competitors in recognition by H-2-restricted cytolytic T cells specific for HLA. J Exp Med. 1988 Apr 1;167(4):1391–1405. doi: 10.1084/jem.167.4.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maryanski J. L., Pala P., Corradin G., Jordan B. R., Cerottini J. C. H-2-restricted cytolytic T cells specific for HLA can recognize a synthetic HLA peptide. Nature. 1986 Dec 11;324(6097):578–579. doi: 10.1038/324578a0. [DOI] [PubMed] [Google Scholar]
  15. McMichael A. J., Gotch F. M., Rothbard J. HLA B37 determines an influenza A virus nucleoprotein epitope recognized by cytotoxic T lymphocytes. J Exp Med. 1986 Nov 1;164(5):1397–1406. doi: 10.1084/jem.164.5.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Oldstone M. B., Whitton J. L., Lewicki H., Tishon A. Fine dissection of a nine amino acid glycoprotein epitope, a major determinant recognized by lymphocytic choriomeningitis virus-specific class I-restricted H-2Db cytotoxic T lymphocytes. J Exp Med. 1988 Aug 1;168(2):559–570. doi: 10.1084/jem.168.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pala P., Bodmer H. C., Pemberton R. M., Cerottini J. C., Maryanski J. L., Askonas B. A. Competition between unrelated peptides recognized by H-2-Kd restricted T cells. J Immunol. 1988 Oct 1;141(7):2289–2294. [PubMed] [Google Scholar]
  18. Parham P., Lomen C. E., Lawlor D. A., Ways J. P., Holmes N., Coppin H. L., Salter R. D., Wan A. M., Ennis P. D. Nature of polymorphism in HLA-A, -B, and -C molecules. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4005–4009. doi: 10.1073/pnas.85.11.4005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rothbard J. B., Lechler R. I., Howland K., Bal V., Eckels D. D., Sekaly R., Long E. O., Taylor W. R., Lamb J. R. Structural model of HLA-DR1 restricted T cell antigen recognition. Cell. 1988 Feb 26;52(4):515–523. doi: 10.1016/0092-8674(88)90464-3. [DOI] [PubMed] [Google Scholar]
  20. Rothbard J. B., Taylor W. R. A sequence pattern common to T cell epitopes. EMBO J. 1988 Jan;7(1):93–100. doi: 10.1002/j.1460-2075.1988.tb02787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Taylor P. M., Davey J., Howland K., Rothbard J. B., Askonas B. A. Class I MHC molecules rather than other mouse genes dictate influenza epitope recognition by cytotoxic T cells. Immunogenetics. 1987;26(4-5):267–272. doi: 10.1007/BF00346521. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Watts T. H., McConnell H. M. High-affinity fluorescent peptide binding to I-Ad in lipid membranes. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9660–9664. doi: 10.1073/pnas.83.24.9660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]

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