Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1993 May;67(5):2887–2893. doi: 10.1128/jvi.67.5.2887-2893.1993

Conservation of determinants for class II-restricted T cells within site E of influenza virus hemagglutinin and factors influencing their expression.

L E Brown 1, D O White 1, D C Jackson 1
PMCID: PMC237614  PMID: 7682631

Abstract

The determinants recognized by helper T cells specific for the site E region of H3 subtype influenza virus hemagglutinin (HA) have been defined by examining the reactivity of T-cell clones with sets of overlapping peptides of various lengths covering the site. Two overlapping sequences, TLIDALLG and LIDALLGDP, were identified as the minimal determinants for four of five representative clones. These sequences are located within a loop of the molecule closed by a disulfide bond and presumably require cleavage of this bond for interaction with the class II major histocompatibility molecule. In contrast, the determinant recognized by the fifth clone was dependent on the presence of an intact disulfide bond for its expression and could not be represented by a synthetic peptide homolog of the linear sequence. Both TLIDALLG and LIDALLGDP are conserved within all field strains of the H3 subtype. Nevertheless, recognition of these sequences by the T-cell clones is affected by the glycosylation pattern of the hemagglutinin and by residues lying outside the minimal determinant. Three distinct clones directed towards the sequence LIDALLGDP were remarkably similar in their pattern of response to a set of synthetic analogs of the determinant, suggesting that residues of the T-cell receptor other than those contacting the minimal determinant may be responsible for the different specificities observed for these clones with different field strains of virus.

Full text

PDF
2887

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adorini L., Appella E., Doria G., Nagy Z. A. Mechanisms influencing the immunodominance of T cell determinants. J Exp Med. 1988 Dec 1;168(6):2091–2104. doi: 10.1084/jem.168.6.2091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allen P. M., Unanue E. R. Differential requirements for antigen processing by macrophages for lysozyme-specific T cell hybridomas. J Immunol. 1984 Mar;132(3):1077–1079. [PubMed] [Google Scholar]
  3. Barnett B. C., Burt D. S., Graham C. M., Warren A. P., Skehel J. J., Thomas D. B. I-Ad restricted T cell recognition of influenza hemagglutinin. Synthetic peptides identify multiple epitopes corresponding to antibody-binding regions of the HA1 subunit. J Immunol. 1989 Oct 15;143(8):2663–2669. [PubMed] [Google Scholar]
  4. Berzofsky J. A., Brett S. J., Streicher H. Z., Takahashi H. Antigen processing for presentation to T lymphocytes: function, mechanisms, and implications for the T-cell repertoire. Immunol Rev. 1988 Dec;106:5–31. doi: 10.1111/j.1600-065x.1988.tb00771.x. [DOI] [PubMed] [Google Scholar]
  5. Brand C. M., Skehel J. J. Crystalline antigen from the influenza virus envelope. Nat New Biol. 1972 Aug 2;238(83):145–147. doi: 10.1038/newbio238145a0. [DOI] [PubMed] [Google Scholar]
  6. Brown L. E., Ffrench R. A., Gawler J. M., Jackson D. C., Dyall-Smith M. L., Anders E. M., Tregear G. W., Duncan L., Underwood P. A., White D. O. Distinct epitopes recognized by I-Ad-restricted T-cell clones within antigenic site E on influenza virus hemagglutinin. J Virol. 1988 Jan;62(1):305–312. doi: 10.1128/jvi.62.1.305-312.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brown L. E., Jackson D. C., Tribbick G., White D. O., Geysen H. M. Extension of a minimal T cell determinant allows relaxation of the requirement for particular residues within the determinant. Int Immunol. 1991 Dec;3(12):1307–1313. doi: 10.1093/intimm/3.12.1307. [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. Bächi T., Gerhard W., Yewdell J. W. Monoclonal antibodies detect different forms of influenza virus hemagglutinin during viral penetration and biosynthesis. J Virol. 1985 Aug;55(2):307–313. doi: 10.1128/jvi.55.2.307-313.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Collins D. S., Unanue E. R., Harding C. V. Reduction of disulfide bonds within lysosomes is a key step in antigen processing. J Immunol. 1991 Dec 15;147(12):4054–4059. [PubMed] [Google Scholar]
  11. Cresswell P. Chemistry and functional role of the invariant chain. Curr Opin Immunol. 1992 Feb;4(1):87–92. doi: 10.1016/0952-7915(92)90131-w. [DOI] [PubMed] [Google Scholar]
  12. Drummer H. E., Jackson D. C., Brown L. E. Modulation of CD4+ T-cell recognition of influenza hemagglutinin by carbohydrate side chains located outside a T-cell determinant. Virology. 1993 Jan;192(1):282–289. doi: 10.1006/viro.1993.1031. [DOI] [PubMed] [Google Scholar]
  13. Falk K., Rötzschke O., Stevanović S., Jung G., Rammensee H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. doi: 10.1038/351290a0. [DOI] [PubMed] [Google Scholar]
  14. Gammon G., Shastri N., Cogswell J., Wilbur S., Sadegh-Nasseri S., Krzych U., Miller A., Sercarz E. The choice of T-cell epitopes utilized on a protein antigen depends on multiple factors distant from, as well as at the determinant site. Immunol Rev. 1987 Aug;98:53–73. doi: 10.1111/j.1600-065x.1987.tb00519.x. [DOI] [PubMed] [Google Scholar]
  15. Gerhard W., Haberman A. M., Scherle P. A., Taylor A. H., Palladino G., Caton A. J. Identification of eight determinants in the hemagglutinin molecule of influenza virus A/PR/8/34 (H1N1) which are recognized by class II-restricted T cells from BALB/c mice. J Virol. 1991 Jan;65(1):364–372. doi: 10.1128/jvi.65.1.364-372.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hunt D. F., Michel H., Dickinson T. A., Shabanowitz J., Cox A. L., Sakaguchi K., Appella E., Grey H. M., Sette A. Peptides presented to the immune system by the murine class II major histocompatibility complex molecule I-Ad. Science. 1992 Jun 26;256(5065):1817–1820. doi: 10.1126/science.1319610. [DOI] [PubMed] [Google Scholar]
  17. Maeji N. J., Bray A. M., Geysen H. M. Multi-pin peptide synthesis strategy for T cell determinant analysis. J Immunol Methods. 1990 Nov 6;134(1):23–33. doi: 10.1016/0022-1759(90)90108-8. [DOI] [PubMed] [Google Scholar]
  18. Margalit H., Spouge J. L., Cornette J. L., Cease K. B., Delisi C., Berzofsky J. A. Prediction of immunodominant helper T cell antigenic sites from the primary sequence. J Immunol. 1987 Apr 1;138(7):2213–2229. [PubMed] [Google Scholar]
  19. Matlin K. S., Reggio H., Helenius A., Simons K. Infectious entry pathway of influenza virus in a canine kidney cell line. J Cell Biol. 1981 Dec;91(3 Pt 1):601–613. doi: 10.1083/jcb.91.3.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Peterson M., Miller J. Antigen presentation enhanced by the alternatively spliced invariant chain gene product p41. Nature. 1992 Jun 18;357(6379):596–598. doi: 10.1038/357596a0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Rudensky AYu, Preston-Hurlburt P., Hong S. C., Barlow A., Janeway C. A., Jr Sequence analysis of peptides bound to MHC class II molecules. Nature. 1991 Oct 17;353(6345):622–627. doi: 10.1038/353622a0. [DOI] [PubMed] [Google Scholar]
  23. Schwartz R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol. 1985;3:237–261. doi: 10.1146/annurev.iy.03.040185.001321. [DOI] [PubMed] [Google Scholar]
  24. Sette A., Buus S., Appella E., Smith J. A., Chesnut R., Miles C., Colon S. M., Grey H. M. Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis. Proc Natl Acad Sci U S A. 1989 May;86(9):3296–3300. doi: 10.1073/pnas.86.9.3296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shimonkevitz R., Colon S., Kappler J. W., Marrack P., Grey H. M. Antigen recognition by H-2-restricted T cells. II. A tryptic ovalbumin peptide that substitutes for processed antigen. J Immunol. 1984 Oct;133(4):2067–2074. [PubMed] [Google Scholar]
  26. Skehel J. J., Stevens D. J., Daniels R. S., Douglas A. R., Knossow M., Wilson I. A., Wiley D. C. A carbohydrate side chain on hemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1779–1783. doi: 10.1073/pnas.81.6.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Unanue E. R. Cellular studies on antigen presentation by class II MHC molecules. Curr Opin Immunol. 1992 Feb;4(1):63–69. doi: 10.1016/0952-7915(92)90127-z. [DOI] [PubMed] [Google Scholar]
  28. Watts T. H., Brian A. A., Kappler J. W., Marrack P., McConnell H. M. Antigen presentation by supported planar membranes containing affinity-purified I-Ad. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7564–7568. doi: 10.1073/pnas.81.23.7564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Werdelin O., Mouritsen S., Petersen B. L., Sette A., Buus S. Facts on the fragmentation of antigens in presenting cells, on the association of antigen fragments with MHC molecules in cell-free systems, and speculation on the cell biology of antigen processing. Immunol Rev. 1988 Dec;106:181–193. doi: 10.1111/j.1600-065x.1988.tb00779.x. [DOI] [PubMed] [Google Scholar]
  30. Yoshimura A., Ohnishi S. Uncoating of influenza virus in endosomes. J Virol. 1984 Aug;51(2):497–504. doi: 10.1128/jvi.51.2.497-504.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES