Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1996 Jul;88(3):348–354. doi: 10.1046/j.1365-2567.1996.d01-673.x

Immunogenicity of peptides for B cells is not impaired by overlapping T-cell epitope topology.

D P Harris 1, H M Vordermeier 1, A Arya 1, K Bogdan 1, C Moreno 1, J Ivanyi 1
PMCID: PMC1456338  PMID: 8774349

Abstract

The epitope specificity of T-cell help to B cells and of surface immunoglobulin-mediated B-cell-binding of antigens usually involves topographically distinct antigenic determinants. The possibility of cross-recognition of the same peptide sequence by both T cells and antibodies has been a matter of conflicting opinions. We investigated this subject by detailed mapping of T- and B-cell epitopes within four immunogenic mycobacterial peptides. The identified core sequences of T- and B-cell epitopes showed different topology within each peptide: they were partially overlapping or adjacent in two P38-derived peptides, but entirely overlapping in two P19-derived peptides. The critically important result using the two truncated peptides (P19/67-78 and P19/146-155) containing only the fully overlapping epitope cores was, that they retained full potency for inducing antibody responses. However, despite this desirable overlap of determinants, antipeptide sera failed to block the proliferation of corresponding T-cell hybridomas. We conclude, that our study, in contrast to previous findings, suggests that overlapping topology of T- and B-cell epitopes within synthetic peptides does not necessarily impair B-cell immunogenicity.

Full text

PDF
348

Images in this article

351Figure 2
on p.351
352Figure 4
on p.352

Selected References

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

  1. Barnett B. C., Graham C. M., Burt D. S., Skehel J. J., Thomas D. B. 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. 1989 Mar;19(3):515–521. doi: 10.1002/eji.1830190316. [DOI] [PubMed] [Google Scholar]
  2. Benjamin D. C., Berzofsky J. A., East I. J., Gurd F. R., Hannum C., Leach S. J., Margoliash E., Michael J. G., Miller A., Prager E. M. The antigenic structure of proteins: a reappraisal. Annu Rev Immunol. 1984;2:67–101. doi: 10.1146/annurev.iy.02.040184.000435. [DOI] [PubMed] [Google Scholar]
  3. Berzofsky J. A. T-B reciprocity. An Ia-restricted epitope-specific circuit regulating T cell-B cell interaction and antibody specificity. Surv Immunol Res. 1983;2(3):223–229. doi: 10.1007/BF02918417. [DOI] [PubMed] [Google Scholar]
  4. Coffman R. L., Seymour B. W., Lebman D. A., Hiraki D. D., Christiansen J. A., Shrader B., Cherwinski H. M., Savelkoul H. F., Finkelman F. D., Bond M. W. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev. 1988 Feb;102:5–28. doi: 10.1111/j.1600-065x.1988.tb00739.x. [DOI] [PubMed] [Google Scholar]
  5. Comerford S. A., McCance D. J., Dougan G., Tite J. P. Identification of T- and B-cell epitopes of the E7 protein of human papillomavirus type 16. J Virol. 1991 Sep;65(9):4681–4690. doi: 10.1128/jvi.65.9.4681-4690.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Corradin G., Engers H. D. Inhibition of antigen-induced T-cell clone proliferation by antigen-specific antibodies. Nature. 1984 Apr 5;308(5959):547–548. doi: 10.1038/308547a0. [DOI] [PubMed] [Google Scholar]
  7. Croft M., Bradley L. M., Swain S. L. Naive versus memory CD4 T cell response to antigen. Memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells. J Immunol. 1994 Mar 15;152(6):2675–2685. [PubMed] [Google Scholar]
  8. Croft M., Swain S. L. B cell response to T helper cell subsets. II. Both the stage of T cell differentiation and the cytokines secreted determine the extent and nature of helper activity. J Immunol. 1991 Dec 1;147(11):3679–3689. [PubMed] [Google Scholar]
  9. Croft M., Swain S. L. B cell response to fresh and effector T helper cells. Role of cognate T-B interaction and the cytokines IL-2, IL-4, and IL-6. J Immunol. 1991 Jun 15;146(12):4055–4064. [PubMed] [Google Scholar]
  10. Fox B. S., Carbone F. R., Germain R. N., Paterson Y., Schwartz R. H. Processing of a minimal antigenic peptide alters its interaction with MHC molecules. Nature. 1988 Feb 11;331(6156):538–540. doi: 10.1038/331538a0. [DOI] [PubMed] [Google Scholar]
  11. Fremont D. H., Matsumura M., Stura E. A., Peterson P. A., Wilson I. A. Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. Science. 1992 Aug 14;257(5072):919–927. doi: 10.1126/science.1323877. [DOI] [PubMed] [Google Scholar]
  12. Garbe T., Harris D., Vordermeier M., Lathigra R., Ivanyi J., Young D. Expression of the Mycobacterium tuberculosis 19-kilodalton antigen in Mycobacterium smegmatis: immunological analysis and evidence of glycosylation. Infect Immun. 1993 Jan;61(1):260–267. doi: 10.1128/iai.61.1.260-267.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Graham C. M., Barnett B. C., Hartlmayr I., Burt D. S., Faulkes R., Skehel J. J., Thomas D. B. 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. 1989 Mar;19(3):523–528. doi: 10.1002/eji.1830190317. [DOI] [PubMed] [Google Scholar]
  14. Grewal I. S., Moudgil K. D., Sercarz E. E. Hindrance of binding to class II major histocompatibility complex molecules by a single amino acid residue contiguous to a determinant leads to crypticity of the determinant as well as lack of response to the protein antigen. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1779–1783. doi: 10.1073/pnas.92.5.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hachimura S., Enomoto A., Kaminogawa S. Relative positioning of the T cell and B cell determinants on an immunogenic peptide: its influence on antibody response. Biochem Biophys Res Commun. 1990 Jun 15;169(2):803–808. doi: 10.1016/0006-291x(90)90402-9. [DOI] [PubMed] [Google Scholar]
  16. Harris D. P., Vordermeier H. M., Arya A., Moreno C., Ivanyi J. Permissive recognition of a mycobacterial T-cell epitope: localization of overlapping epitope core sequences recognized in association with multiple major histocompatibility complex class II I-A molecules. Immunology. 1995 Apr;84(4):555–561. [PMC free article] [PubMed] [Google Scholar]
  17. Harris D. P., Vordermeier H. M., Brett S. J., Pasvol G., Moreno C., Ivanyi J. Epitope specificity and isoforms of the mycobacterial 19-kilodalton antigen. Infect Immun. 1994 Jul;62(7):2963–2972. doi: 10.1128/iai.62.7.2963-2972.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Harris D. P., Vordermeier H. M., Roman E., Lathigra R., Brett S. J., Moreno C., Ivanyi J. Murine T cell-stimulatory peptides from the 19-kDa antigen of Mycobacterium tuberculosis. Epitope-restricted homology with the 28-kDa protein of Mycobacterium leprae. J Immunol. 1991 Oct 15;147(8):2706–2712. [PubMed] [Google Scholar]
  19. Inaba K., Steinman R. M., Van Voorhis W. C., Muramatsu S. Dendritic cells are critical accessory cells for thymus-dependent antibody responses in mouse and in man. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6041–6045. doi: 10.1073/pnas.80.19.6041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kovac Z., Schwartz R. H. The molecular basis of the requirement for antigen processing of pigeon cytochrome c prior to T cell activation. J Immunol. 1985 May;134(5):3233–3240. [PubMed] [Google Scholar]
  21. Kurisaki J., Atassi H., Atassi M. Z. T cell recognition of ragweed allergen Ra3: localization of the full T cell recognition profile by synthetic overlapping peptides representing the entire protein chain. Eur J Immunol. 1986 Mar;16(3):236–240. doi: 10.1002/eji.1830160305. [DOI] [PubMed] [Google Scholar]
  22. Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. doi: 10.1038/314537a0. [DOI] [PubMed] [Google Scholar]
  23. Lassila O., Vainio O., Matzinger P. Can B cells turn on virgin T cells? Nature. 1988 Jul 21;334(6179):253–255. doi: 10.1038/334253a0. [DOI] [PubMed] [Google Scholar]
  24. Lehner T., Walker P., Bergmeier L. A., Haron J. A. Immunogenicity of synthetic peptides derived from the sequences of a Streptococcus mutans cell surface antigen in nonhuman primates. J Immunol. 1989 Oct 15;143(8):2699–2705. [PubMed] [Google Scholar]
  25. 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]
  26. Manca F., Fenoglio D., Kunkl A., Cambiaggi C., Sasso M., Celada F. Differential activation of T cell clones stimulated by macrophages exposed to antigen complexed with monoclonal antibodies. A possible influence of paratope specificity on the mode of antigen processing. J Immunol. 1988 May 1;140(9):2893–2898. [PubMed] [Google Scholar]
  27. Nicholas J. A., Mitchell M. A., Levely M. E., Rubino K. L., Kinner J. H., Harn N. K., Smith C. W. Mapping an antibody-binding site and a T-cell-stimulating site on the 1A protein of respiratory syncytial virus. J Virol. 1988 Dec;62(12):4465–4473. doi: 10.1128/jvi.62.12.4465-4473.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nygard N. R., Bono C., Brown L. R., Gorka J., Giacoletto K. S., Schaiff W. T., Graham M. B., McCourt D. W., Kabeer M., Braciale V. L. Antibody recognition of an immunogenic influenza hemagglutinin-human leukocyte antigen class II complex. J Exp Med. 1991 Jul 1;174(1):243–251. doi: 10.1084/jem.174.1.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ozaki S., Berzofsky J. A. Antibody conjugates mimic specific B cell presentation of antigen: relationship between T and B cell specificity. J Immunol. 1987 Jun 15;138(12):4133–4142. [PubMed] [Google Scholar]
  30. Reth M. Antigen receptors on B lymphocytes. Annu Rev Immunol. 1992;10:97–121. doi: 10.1146/annurev.iy.10.040192.000525. [DOI] [PubMed] [Google Scholar]
  31. Rothbard J. B., Gefter M. L. Interactions between immunogenic peptides and MHC proteins. Annu Rev Immunol. 1991;9:527–565. doi: 10.1146/annurev.iy.09.040191.002523. [DOI] [PubMed] [Google Scholar]
  32. Sakurai T., Ametani A., Nakamura Y., Shimizu M., Idota T., Kaminogawa S. Cryptic B cell determinant in a short peptide: T cells do not induce antibody response of B cells when their determinants entirely overlap each other. Int Immunol. 1993 Jul;5(7):793–800. doi: 10.1093/intimm/5.7.793. [DOI] [PubMed] [Google Scholar]
  33. Simitsek P. D., Campbell D. G., Lanzavecchia A., Fairweather N., Watts C. Modulation of antigen processing by bound antibodies can boost or suppress class II major histocompatibility complex presentation of different T cell determinants. J Exp Med. 1995 Jun 1;181(6):1957–1963. doi: 10.1084/jem.181.6.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stern L. J., Brown J. H., Jardetzky T. S., Gorga J. C., Urban R. G., Strominger J. L., Wiley D. C. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature. 1994 Mar 17;368(6468):215–221. doi: 10.1038/368215a0. [DOI] [PubMed] [Google Scholar]
  35. Unanue E. R., Allen P. M. The basis for the immunoregulatory role of macrophages and other accessory cells. Science. 1987 May 1;236(4801):551–557. doi: 10.1126/science.2437650. [DOI] [PubMed] [Google Scholar]
  36. Vordemeier H. M., Harris D. P., Roman E., Lathigra R., Moreno C., Ivanyi J. Identification of T cell stimulatory peptides from the 38-kDa protein of Mycobacterium tuberculosis. J Immunol. 1991 Aug 1;147(3):1023–1029. [PubMed] [Google Scholar]
  37. Vordermeier H. M., Harris D. P., Moreno C., Singh M., Ivanyi J. The nature of the immunogen determines the specificity of antibodies and T cells to selected peptides of the 38 kDa mycobacterial antigen. Int Immunol. 1995 Apr;7(4):559–566. doi: 10.1093/intimm/7.4.559. [DOI] [PubMed] [Google Scholar]
  38. Watson J. Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. J Exp Med. 1979 Dec 1;150(6):1510–1519. doi: 10.1084/jem.150.6.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Watts C., Lanzavecchia A. Suppressive effect of antibody on processing of T cell epitopes. J Exp Med. 1993 Oct 1;178(4):1459–1463. doi: 10.1084/jem.178.4.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES