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Immunogenicity of free synthetic peptides corresponding to T helper epitopes of the influenza HA 1 subunit

Induction of virus cross reacting CD 4+ T lymphocytes in mice

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Summary

Four linear synthetic peptides corresponding to residues 12–29, 50–67, 121–138 and 131–147 of the HA 1 subunit of H 3 subtype influenza virus (NT/60/68) were tested for their capacity to elicit in vivo peptide-specific CD 4+ T cells cross reacting with whole virus.

By studying the in vitro peptide proliferative response of lymph node cells from mice sensitized in vivo with free peptides emulsified in complete or incomplete Freund adjuvant, it was found that region 12–29 could be recognized by CD 4+ T lymphocytes in the context of H-2k and H-2b, region 50–67 in association with H-2b and region 121–138 in the context of H-2d MHC molecules. Outbred OF 1 mice could recognize regions 50–67 and 121–138.

Peptides 50–67 and 121–138 are of potential interest for synthetic vaccine design since they induced in BALB/c (peptide 121–138) and OF 1 (both peptides) mice a CD 4+ T cell population that cross reacted with whole virus. The region 50–67 is of particular interest since only few substitutions have been found in this area in natural variants of the H 3 virus subtype.

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References

  1. Adorini L, Muller S, Cardinaux F, Lehmann PV, Falcioni F, Nagy ZA (1988) In vivo competition between self peptides and foreign antigens in T-cell activation. Nature 334: 623–625

    Google Scholar 

  2. Babbit BP, Allen PM, Matsueda G, Haber E, Uranue ER (1985) Binding of immunogenic peptides to la histocompatibility molecules. Nature 317: 359–361

    Google Scholar 

  3. Barnett BC, Burt DS, Graham CM, Warren AP, Skehel JJ, Thomas DB (1989) I-Ad restricted T cell recognition of influenza hemagglutinin. Synthetic peptides identify multiples epitopes corresponding to antibody-binding regions of the HA 1 subunit. J Immunol 143: 2663–2669

    Google Scholar 

  4. Barnett BC, Graham CM, Burt DS, Skehel JJ, Thomas DB (1989) The immune response of BALB/c mice to influenza hemagglutinin: commonality of the B cell and T cell repertoires and their relevance to antigenic drift. Eur J Immunol 19: 515–521

    Google Scholar 

  5. Bixler GS Jr, Atassi MZ (1985) Antigen presentation of myoglobin: profiles of T cell proliferative responses following priming with synthetic overlapping peptides encompassing the entire molecule. Eur J Immunol 15: 917–922

    Google Scholar 

  6. Brett SJ, Cease KB, Berzofsky JA (1988) Influences of antigen processing on the expression of the T cell repertoire. Evidence for MHC-specific hindering structures on the products of processing. J Exp Med 168: 357–373

    Google Scholar 

  7. Brown LE, Ffrench RA, Gawler JM, Jackson DC, Dyall-Smith ML, Anders EM, Tregear GW, Duncan L, Underwood PA, White DO (1988) Distinct epitopes recognized by I-A-restricted T-cell clones within antigenic site E on influenza virus hemagglutinin. J Virol 62: 305–312

    Google Scholar 

  8. Buchmüller Y, Corradin G (1982) Lymphocyte specificity to protein antigens V. Conformational dependence of activation of cytochrome c-specific T cells. Eur J Immunol 12: 412–416

    Google Scholar 

  9. Burt DS, Mills KHG, Skehel JJ, Thomas DB (1989) Diversity of the class II (I-Ak/I-Ek)-restricted T cell repertoire for influenza hemagglutinin and antigenic drift. J Exp Med 170: 383–397

    Google Scholar 

  10. Corradin G, Etlinger HM, Chiller JM (1977) Lymphocyte specificity to protein antigens. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice. J Immunol 119: 1048–1053

    Google Scholar 

  11. Corradin G, Lanzavecchia A (1991) Chemical and functional analysis of MHC class II-restricted T cell epitopes. Int Rev Immunol 7: 139–147

    Google Scholar 

  12. Demotz S, Matricardi PM, Irle C, Panina P, Lanzavecchia A, Corradin G (1989) Processing of tetanus toxin by human antigen-presenting cells. Evidence for donor and epitope-specific processing pathways. J Immunol 143: 3881–1886

    Google Scholar 

  13. Eisenlohr LC, Gerhard W, Hackett CJ (1987) Role of receptor binding activity of the viral haemagglutinin molecule in the presentation of influenza virus antigens to helper T cells. J Virol 61: 1375–1383

    Google Scholar 

  14. Eisenlohr LC, Gerhard W, Hackett CJ (1988) Acid-induced conformational modification of the hemagglutinin molecule alters interaction of influenza virus with antigen-presenting cells. J Immunol 141: 1870–1876

    Google Scholar 

  15. EMBO (1983) Course on antigen specific T cell lines. Centre d'Immunologie INSERMCNRS, Marseille-Luminy, France, 1983, May 1–12

    Google Scholar 

  16. Ffrench RA, Tang X, Anders EM, Jackson DC, White DO, Drummer H, Wade JD, Tregear GW, Brown LE (1989) Class II-restricted T-cell clones to a synthetic peptide of influenza virus hemagglutinin differ in their fine specificities and in the ability to respond to virus. J Virol 63: 3087–3094

    Google Scholar 

  17. Gerhard W, Haberman AM, Scherle PA, Taylor AH, Palladino G, Caton AJ (1991) 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 65: 364–372

    Google Scholar 

  18. Gerhard W, Hackett C, Melchers F (1983) The recognition specificity of a murine helper T cell for hemagglutinin of influenza virus A/PR/8/34. J Immunol 130: 2379–2385

    Google Scholar 

  19. Graham CM, Barnett BC, Hartlmayr I, Burt DS, Faulkes R, Skehel JJ, Thomas DB (1989) The structural requirements for class II (I-Ad)-restricted T cell recognition of influenza hemagglutinin: B cell epitopes define T cell epitopes. Eur J Immunol 19: 523–528

    Google Scholar 

  20. Hackett CJ, Dietzschold B, Gerhard W, Ghrist B, Knorr R, Gillessen D, Melchers F (1983) Influenza virus site recognized by a murine helper T cell specific for H 1 strains. Localization to a nine amino acid sequence in the hemagglutinin molecule. J Exp Med 158: 294–302

    Google Scholar 

  21. Hackett CJ, Hurwitz JL, Dietzschold B, Gerhard W (1985) A synthetic decapeptide of influenza virus hemagglutinin elicits helper T cells with the same fine recognition specificities as occur in response to whole virus. J Immunol 135: 1391–1394

    Google Scholar 

  22. Hurwitz JL, Heber-Katz E, Hackett CJ, Gerhard W (1984) Characterization of the murine Th response to influenza virus hemagglutinin: evidence for three major specificities. J Immunol 133: 3371–3377

    Google Scholar 

  23. Lamb JR, Eckels DD, Lake P, Woody JN, Green N (1982) Human T-cell clones recognize chemically synthetized peptides of influenza hemagglutinin. Nature 300: 66–68

    Google Scholar 

  24. Laver WG, Webster RG (1966) The structure of influenza viruses. 4. Chemical studies of the host antigen. Virology 30: 104–115

    Google Scholar 

  25. Michalek MT, Benacerraf B, Rock KL (1989) Two genetically identical antigen-presenting cell clones display heterogeneity in antigen processing. Proc Natl Acad Sci USA 86: 3316–3320

    Google Scholar 

  26. Mills KHG, Skehel JJ, Thomas DB (1986) Conformational-dependent recognition of influenza virus hemagglutinin by murine T helper clones. Eur J Immunol 16: 276–280

    Google Scholar 

  27. Mills KHG, Skehel JJ, Thomas DB (1986) Extensive diversity in the recognition of influenza virus hemagglutinin by murine T helper clones. J Exp Med 163: 1477–1490

    Google Scholar 

  28. Mills KHG, Burt DS, Skehel JJ, Thomas DB (1988) Fine specificity of murine class II-restricted T cell clones for synthetic peptides of influenza virus hemagglutinin. J Immunol 140: 4083–4090

    Google Scholar 

  29. Muller S, Plaue S, Samama JP, Valette M, Briand JP, Van Regenmortel MHV (1990) Antigenic properties and protective capacity of a cyclic peptide corresponding to site A of influenza virus hemagglutinin. Vaccine 8: 308–314

    Google Scholar 

  30. Rothbard JB, Taylor WR (1988) A sequence pattern common to T cell epitopes. EMBO J 7: 93–100

    Google Scholar 

  31. Scherle PA, Gerhard W (1986) Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal virus proteins provide cognate help for B cell responses to hemagglutinin. J Exp Med 164: 1114–1128

    Google Scholar 

  32. Thomas DB, Skehel JJ, Mills KHG, Graham CM (1986) Suicide selection of murine T helper clones specific for variable regions of the influenza hemagglutinin molecule. Eur J Immunol 16: 789–793

    Google Scholar 

  33. Thomas DB, Skehel JJ, Mills KHG, Graham CM (1987) A single amino acid substitution in influenza hemagglutinin abrogates recognition by monoclonal antibody and a spectrum of subtype-specific L3T4 (+) T cell clones. Eur J Immunol 17: 133–136

    Google Scholar 

  34. Van Regenmortel MHV, Briand JP, Muller S, Plaue S (1988) Synthetic polypeptides as antigens. Laboratory techniques in biochemistry and molecular biology, vol 19. Elsevier, Amsterdam

    Google Scholar 

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Schneider, C., Van Regenmortel, M.H.V. Immunogenicity of free synthetic peptides corresponding to T helper epitopes of the influenza HA 1 subunit. Archives of Virology 125, 103–119 (1992). https://doi.org/10.1007/BF01309631

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  • DOI: https://doi.org/10.1007/BF01309631

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