Skip to main content

Autoantibodies Against Peptide-Defined Epitopes of T-Cell Receptors in Retrovirally Infected Humans and Mice

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 383))

Abstract

Autoantibodies directed against peptide-defined epitopes of T-cell receptors occur in the serum of healthy humans with the levels and isotypic expression dependent upon physiological changes (aging, pregnancy) or upon the development of autoimmune disease. We carried out investigations of autoantibodies against Tcr peptide-defined epitopes in retroviral infections of humans (HIV-1) and mice (LP-BM5 strain of murine leukemia virus) to determine whether infection with these agents disrupted the regulation of the production of these antibodies. Retroviral infection in humans resulted in increased levels of autoantibody production against putative immunoregulatory regions of the Tcr ß chain (Vß CDR1 and Fr3), a result reflecting a disruption of regulation. In addition, antigenic mimicry was observed with a cross-reaction shared between the common portion of the V3 neutralizing loop of the HIV-1 gp 120 molecule and the joining segment of T-cell receptors (Jß). Infection of mice with the defective retrovirus resulted in the induction of antibodies directed particularly against Vß CDR1 peptide-defined determinants. Analysis of the virally induced response to a set of 8 CDR1 peptide epitopes indicated a selectivity to the process. It was possible to partially reverse aberrant cytokine changes correlated with the onset of murine MAIDS by administration of T-cell receptor peptides in saline. These results show that retroviral infection in humans and mice has a profound dysfunctional effect on the regulation of autoantibodies to T-cell receptors. The function of these autoantibodies in the immunopathogenesis of acquired immunodeficiency remains to be determined.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Fauci, A.S., 1993, Multifactorial nature of human immunodeficiency virus disease: implications for therapy. Science 262:1011–1016

    Article  PubMed  CAS  Google Scholar 

  2. Valentine, F.T., 1990, Pathogenesis of the immunological deficiences caused by infection with the human immunodeficiency virus. Seminars in Oncology 17:321–334.

    PubMed  CAS  Google Scholar 

  3. Clerici, M., Shearer, G., Hounsell, E.F., Jameson, B., Habeshaw, J. and Dalgleish, A.G., 1993, Alloactivated cytotoxic T cells recognize the carboxy terminal domain of human immunodeficiency virus-1 gp 120 envelope glycoprotein. Eur. J. Immunol. 23:2022–2025.

    Article  PubMed  CAS  Google Scholar 

  4. Katz, D.H., 1993, AIDS: Primarily a viral or an autoimmune Disease? AIDS Resch and Human Retroviruses. 9:489–493.

    Article  CAS  Google Scholar 

  5. Kion, T.A. and Hoffman, G.W., 1991, Anti-HIV and anti-MHC antibodies in alloimmune and autoimmune mice. Science 253:1138–1140.

    Article  PubMed  CAS  Google Scholar 

  6. Marchalonis, J.J., Kaymaz, H, Dedeoglu, F., Schluter, S.F., Yocum, D.E. and Edmundson, A.B., 1992, Human autoantibodies reactive with synthetic autoantigens from T-cell receptor P. chain. Proc. Natl. Acad. Sci. USA 89:3325–3329.

    Article  PubMed  CAS  Google Scholar 

  7. Marchalonis, J.J., Schluter, S.F., Wilson, L., Yocum, D.E., Boyer, J.R. and Kay, M.M.B., 1993, Natural human antibodies to synthetic peptide autoantigens: correlations with age and autoimmune disease. Geront. 39:65–79.

    Article  CAS  Google Scholar 

  8. Marchalonis, J.J., Kaymaz H, Schluter, S.F., and Yocum, D.E., 1993, Human autoantibodies to a synthetic putative T-cell receptor 3-chain regulatory idiotype: Expression in autoimmunity and aging. Expt. & Clin. Immunogenet. 10:1–15.

    CAS  Google Scholar 

  9. Marchalonis, J.J., Schluter, S.F., Wang, E., Dehghanpisheh, K., Lake, D., Yocum, D.E., Edmundson, A.B. and Winfield, J.B., 1994, Synthetic autoantigens of immunoglobulins and T-cell receptors: their recognition in aging, infection and autoimmunity. Proc. Soc. Expt. Biol. 207:129–147.

    CAS  Google Scholar 

  10. Dedeoglu, F., Kaymaz, H., Klein, G. and Marchalonis, J.J., 1993, Light and heavy chains specifying a human IgM x autoantibody to a T-cell receptor VP-antigen. Immunol. Letts. 38:223–227.

    Article  CAS  Google Scholar 

  11. Pullen A.M., Bill J., Kubo R.T., Marrack P., Kappler J.W., 1991, Analysis of the interaction site for the self-superantigen Mls-1 a on T-cell receptor vp. J. Exp. Med. 173:1183–1185.

    Article  PubMed  CAS  Google Scholar 

  12. Chothia, G., Boswell, D.R. and Lesk, A.M., 1988, The outline structure of the T-cell ap receptor. EMBO J. 7:3745–3755.

    PubMed  CAS  Google Scholar 

  13. Marchalonis, J.J., Dedeoglu. F., Kaymaz, H, Schluter, S.F., and Edmundson, A.B., 1992, Antigenic mapping of a human X light chain: Correlation with 3-dimensional structure. J. Prot. Chem. 11:129–137.

    Article  Google Scholar 

  14. Kaymaz, H. and Marchalonis, J.J., 1993, Autoreactive sites of human ? light chain mapped by comprehensive peptide synthesis. J. Prot. Chem. 12:659–666.

    Article  CAS  Google Scholar 

  15. Marchalonis, J.J., Kaymaz, H., Schluter, S.F. and Yocum, D.E., 1994, Naturally occurring human autoantibodies to defined T-cell receptor and light chain peptides. in Immunobiology of Proteins and Peptides VII. (M.T. Atassi, ed.), Plenum Press, N.Y., pp 135–145.

    Chapter  Google Scholar 

  16. Kaymaz, H., Dedeoglu, F., Schluter, S.F., Edmundson, A.B. and Marchalonis, J.J., 1993, Reactions of anti-immunoglobulin sera with synthetic T-cell receptor peptides: implications for the three-dimensional structure and function of the Tcr P chain. Intl. Immunol. 5:491–502.

    Article  CAS  Google Scholar 

  17. Prince, A.M., Horowitz, B., Baker, L., Shulman, R.W., Ralph, H., Valinsky, J., Cundell, A., Brotman, B., Boehle, W., Rey, F., Piet, M., Teesink, H., Lelie, N., Tersmette, M., Miedema, F., Barbosa, S., Nemo, G., Nastala, C.L., Assan, J.S., Lee, D.R. and Eichberg, J.W., 1988, Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV. Proc. Natl. Acad. Sci. USA 85:6944–6948.

    Article  PubMed  CAS  Google Scholar 

  18. Huang, D.S., Wang, Y., Marchalonis, J.J., and Watson, R.R., 1994, The kinetics of cytokine secretion and proliferation by mesentric lymph node cells during the progression to murine AIDS, caused by LP-BM5 murine leukemia virus infection. Regional Immunol. 5:325–331.

    Google Scholar 

  19. Dehghanpisheh, K., Huang, D., Schluter, S.F., Watson, R.R. and Marchalonis, J.J., 1995, Production of IgG autoantibodies to T-cell receptors in mice infected with the retrovirus LP-BM5.Intl. Immunol. 7: in press.

    Google Scholar 

  20. La Rosa G.J., Davide J.P., Weinhold K., Waterburg J.A., Profy A.T., Lewis J.A., Langlois A.J., Dreesman G.R., Boswell R.N., Shadduck P., Holley L.H., Karplus M., Bolognesi D., Mathews T.J., Emini E.A., and Putney S.D., 1990, Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science 249:932–935.

    Article  Google Scholar 

  21. Schluter, S.F. and Marchalonis, J.J., 1986, Antibodies to synthetic joining segment peptide of the T-cell receptor (3-chain: serological cross-reaction between products of T-cell receptor genes, antigen binding T-cell receptors and immunoglobulins. Proc. Natl. Acad. Sci. USA. 83:1872–1876.

    Article  PubMed  CAS  Google Scholar 

  22. Marchalonis, J.J., Schluter, S.F., Hubbard, R.A., McCabe, C. and Allen, R.C., 1988, Immunoglobulin epitopes defined by synthetic peptides corresponding to joining-region sequence: Conservation of determinants and dependence upon the presence of an arginyl or lysyl residue for cross-reaction between light chains and T cell receptor chains Mol. Immunol. 25:771–784.

    CAS  Google Scholar 

  23. Lake, D.F., Schluter, S.F., Wang, E., Bernstein, R.M., Edmundson, A.B. and Marchalonis, J.J., 1994, Autoantibodies to the a/13 T-cell receptors in human immunodeficiency virus (HIV) infection: dysregulation and mimicry. Proc. Natl. Acad. Sci. USA. 91:10849–10853.

    Article  PubMed  CAS  Google Scholar 

  24. Ghiara, J.B., Stura, E.A., Stanfield, R.L., Profy, A.T., and Wilson, I.A., 1994, Crystal structure of the principal neutralization site of HIV-1. Science 264:82–85.

    Article  PubMed  CAS  Google Scholar 

  25. Jolicoeur P., 1991, Murine acquired immunodeficiency syndrome (MAIDS): an animal model to study the AIDS pathogenesis. FASEB J. 5:2398–2401.

    PubMed  CAS  Google Scholar 

  26. Shankey, T.V., Schluter, S.F. and Marchalonis, J.J., 1989, Flow cytometric analysis of human lymphocytes using affinity purified antibody to T cell receptors synthetic J region. Cell Immunol. 118:526–531.

    Article  PubMed  CAS  Google Scholar 

  27. Carson, D.A., Chen, P.P., Fox, R.I., Kipps, T.J., Jirik, F., Goldfine, R.D., Silverman, G., Radoux, V. and Fong, S., 1987, Rheumatoid factor and immune networks. Ann. Rev. Immunol. 5:109–126.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Marchalonis, J.J. et al. (1995). Autoantibodies Against Peptide-Defined Epitopes of T-Cell Receptors in Retrovirally Infected Humans and Mice. In: Atassi, M.Z., Bixler, G.S. (eds) Immunobiology of Proteins and Peptides VIII. Advances in Experimental Medicine and Biology, vol 383. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1891-4_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1891-4_22

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5771-1

  • Online ISBN: 978-1-4615-1891-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics