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The specific T-cell response to antigenic peptides is influenced by bystander peptides

Abstract

T lymphocytes recognize antigens in the form of peptides presented by major histocompatibility complex (MHC) molecules on the cell surface. Only a small proportion of MHC class I and class II molecules are loaded with foreign antigenic peptides; the vast majority are loaded with thousands of different self peptides. It was suggested that MHC molecules presenting self peptides may serve either to decrease (antagonistic effect) or increase (synergistic effect) the T cell response to a specific antigen. Here, we present our finding that transfected mouse fibroblasts presenting a single antigenic peptide covalently bound to a class II MHC molecule stimulated specific mouse T cell hybridoma cells to an interleukin-2 response less efficiently than fibroblasts presenting a similar amount of antigenic peptide in the presence of class II molecules loaded with heterogenous bystander peptides.

Abbreviations

Abwt:

fibroblasts transfected with wild-type Ab class II MHC molecule

AbEp:

fibroblasts transfected with Ab molecule with linked Ep

Abwt + AbEp:

double transfectant fibroblasts

Ep:

peptide 52-68 from the Eα class II MHC chain

FACS:

fluorescein-activated cell sorter

MHC:

major histocompatibility complex

MTT:

(3-[4,5 dimethylthiazol-2-lyl]-2,5 diphenyl tetrazolium bromide

TCR:

T cell receptor

References

  1. 1.

    Germain, R.N. and Štefanová, I. The dynamics of T cell receptor signalling: Complex orchestration and the key roles of tempo and cooperation. Annu. Rev. Immunol. 17 (1999) 467–522.

    PubMed  CAS  Article  Google Scholar 

  2. 2.

    Marrack, P., Ignatowicz, L., Kappler, J.W., Boymel, J. and Freed, J.H. Comparison of peptides bound to spleen and thymus class II. J. Exp. Med. 178 (1993) 2173–2183.

    PubMed  CAS  Article  Google Scholar 

  3. 3.

    Derbinski, J., Schulte, A., Kyewski, B. and Klein, L. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat. Immunol. 2 (2001) 1032–1039.

    PubMed  CAS  Article  Google Scholar 

  4. 4.

    Wülfing, C., Sumen, C., Sjaastad, M.D., Wu, L.C., Dustin, M.L. and Davis, M.M. Costimulation and endogenous MHC ligands contribute to T cell recognition. Nat. Immunol. 3 (2002) 42–47.

    PubMed  Article  Google Scholar 

  5. 5.

    Sporri, R. and Reis e Sousa, C. Self peptide/MHC class I complexes have a negligible effect on the response of some CD8+ T cells to foreign antigen. Eur. J. Immunol. 32 (2002) 3161–3170.

    PubMed  CAS  Article  Google Scholar 

  6. 6.

    Ignatowicz, L., Winslow, G., Bill, J., Kappler, J. and Marrack, P. Cell surface expression of class II MHC proteins bound by a single peptide. J. Immunol. 154 (1995) 3852–3862.

    PubMed  CAS  Google Scholar 

  7. 7.

    Ignatowicz, L., Rees, W., Pacholczyk, R., Ignatowicz, H., Kushnir, E., Kappler, J. and Marrack, P. T cells can be activated by peptides that are unrelated in sequence to their selecting peptide. Immunity 7 (1997) 179–186.

    PubMed  CAS  Article  Google Scholar 

  8. 8.

    Gillis, S. and Smith, K.A. Long term culture of tumour-specific cytotoxic T cells. Nature 268 (1977) 154–156.

    PubMed  CAS  Article  Google Scholar 

  9. 9.

    Watson, J. Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. J. Exp. Med. 150 (1979) 1510–1519.

    PubMed  CAS  Article  Google Scholar 

  10. 10.

    Pajtasz-Piasecka, E., Kuśnierczyk, H., Salwa, J., Konarski L. and Radzikowski, C. Growth inhibition of transplantable tumors in mice by mIL-2-secreting murine plasmocytoma cells used alone or in combination with a cytostatic agent. Arch. Immunol. Ther. Exp. 43 (1995) 281–292.

    CAS  Google Scholar 

  11. 11.

    Janeway, C.A., Conrad, P., Lerner, E., Babich, J., Wettstein, P. and Murphy, D. Monoclonal antibodies specific for Ia antigens as targets of immunoregulatory T cells. J. Immunol. 132 (1984) 662–669.

    PubMed  Google Scholar 

  12. 12.

    Murphy, D., Lo, D., Rath, S., Brinster, R., Flavel, R., Slanetz, A. and Janeway, C. A novel MHC class II epitope expressed in thymic medulla but not cortex. Nature 338 (1989) 765–768.

    PubMed  CAS  Article  Google Scholar 

  13. 13.

    Ignatowicz, L., Kappler, J. and Marrack, P. The repertoire of T cells selected by a single MHC/peptide ligand. Cell 84 (1996) 521–529.

    PubMed  CAS  Article  Google Scholar 

  14. 14.

    Davis, S.J. and van der Merwe, P.A. TCR triggering: co-receptor-dependent or-independent? Trends Immunol. 24 (2003) 624–626.

    PubMed  CAS  Article  Google Scholar 

  15. 15.

    Greenwald, R.J., Latchman, Y. and Sharpe, A.H. Negative co-receptors on lymphocytes. Curr. Opin. Immunol. 14 (2002) 391–396.

    PubMed  CAS  Article  Google Scholar 

  16. 16.

    Iezzi, G., Karjalainen, K. and Lanzavecchia, A. The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 8 (1998) 89–95.

    PubMed  CAS  Article  Google Scholar 

  17. 17.

    Holzer, U., Kwok, W.W., Nepom, G.T. and Buckner, J.H. Differential antigen sensitivity and costimulatory requirements in human Th1 and Th2 antigen-specific CD4+ cells with similar TCR avidity. J. Immunol. 170 (2003) 1218–1223.

    PubMed  CAS  Google Scholar 

  18. 18.

    Kraj, P., Pacholczyk, R., Ignatowicz, H., Kisielow, P., Jensen, P. and Ignatowicz, L. Positive selection of CD4+ T cells is induced in vivo by agonist and inhibited by antagonist peptides. J. Exp. Med. 194 (2001) 407–416.

    PubMed  CAS  Article  Google Scholar 

  19. 19.

    Viret, C., He, X. and Janeway, C.A. Paradoxical intrathymic positive selection in mice with only a covalently presented agonist peptide. Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 9243–9248.

    PubMed  CAS  Article  Google Scholar 

  20. 20.

    Bouneaud, C., Kourilsky, P. and Bousso, P. Impact of negative selection on the T cell repertoire reactive to a self-peptide; a large fraction of T cell clones escapes clonal deletion. Immunity 13 (2000) 829–840.

    PubMed  CAS  Article  Google Scholar 

  21. 21.

    Yan, J. and Mamula, M.J. Autoreactive T cells revealed in the normal reperoire: escape from negative selection and peripheral tolerance. J. Immunol. 168 (2002) 3188–3194.

    PubMed  CAS  Google Scholar 

  22. 22.

    Cohen, I.R., Hershberg, U. and Solomon, S. Antigen-receptor degeneracy and immunological paradigms. Mol. Immunol. 40 (2004) 993–996.

    PubMed  CAS  Article  Google Scholar 

  23. 23.

    Ford, M.L. and Evavold, B.D. Degenerate recognition of T cell epitopes: impact on T cell receptor reserve and stability of peptide: MHC complexes. Mol. Immunol. 40 (2004) 1019–1025.

    PubMed  CAS  Article  Google Scholar 

  24. 24.

    Sercarz, E.E. and Maverakis, E. Recognition and function in a degenerate immune system. Mol. Immunol. 40 (2004) 1003–1008.

    PubMed  CAS  Article  Google Scholar 

  25. 25.

    Wilson, D.B., Wilson, D.H., Schroder, K., Pinilla, C., Blondelle, S., Houghten, R.A. and Garcia, K.C. Specificity and degeneracy of T cells. Mol. Immunol. 40 (2004) 1047–1055.

    PubMed  CAS  Article  Google Scholar 

  26. 26.

    Thibault, G. and Bardos, P. Compared TCR and CD3ε expression on αβ and γδ T cells. J. Immunol. 154 (1995) 3814–3820.

    PubMed  CAS  Google Scholar 

  27. 27.

    Zapata, D.A., Schamel, W.W.A., Torres, P.S., Alarcón, B., Rossi, N.E., Navarro, M.N., Toribio, M.L., and Regueiro, J.R. Biochemical differences in the alphabeta T cell receptor. CD3 surface complex between CD8+ and CD4+ human mature T lymphocytes. J. Biol. Chem. 279 (2004) 24485–24492.

    PubMed  CAS  Article  Google Scholar 

  28. 28.

    Chmielowski, B., Pacholczyk, R., Kraj, P., Kisielow, P. and Ignatowicz, L. Presentation of antagonist peptides to naive CD4+ T cells abrogates spatial reorganization of class II MHC peptide complexes on the surface of dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 15012–15017.

    PubMed  CAS  Article  Google Scholar 

  29. 29.

    Bakker, T.R. and van der Merve, P.A. Self-help in T cell recognition? Nat. Immunol. 3 (2002) 11–12.

    PubMed  CAS  Article  Google Scholar 

  30. 30.

    Štefanová, I., Dorfman, J.R., Tsukamoto, M. and Germain R.N. On the role of self-recognition in T cell responses to foreign antigen. Immunol. Rev. 191 (2003) 97–106.

    PubMed  Article  Google Scholar 

  31. 31.

    Štefanova, I., Dorfman, J.R. and Germain R.N. Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes. Nature 420 (2002) 429–433.

    PubMed  Article  Google Scholar 

  32. 32.

    Choi, J. and Craft, J. Activation of naive CD4+ T cells in vivo by a self peptide mimic: mechanism of tolerance maintenance and preservation of immunity. J. Immunol. 172 (2004) 7399–7406.

    PubMed  CAS  Google Scholar 

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Correspondence to Piotr Kuśnierczyk.

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Nowak, I., Pajtasz-Piasecka, E., Chmielowski, B. et al. The specific T-cell response to antigenic peptides is influenced by bystander peptides. Cell. Mol. Biol. Lett. 11, 70–79 (2006). https://doi.org/10.2478/s11658-006-0007-5

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Key Words

  • Bystander peptide
  • T cell response
  • Transfectants
  • Mouse model