Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1996 Jun 15;97(12):2849–2858. doi: 10.1172/JCI118741

Immunization with T cell receptor V beta chain peptides deletes pathogenic T cells and prevents the induction of collagen-induced arthritis in mice.

T M Haqqi 1, X M Qu 1, D Anthony 1, J Ma 1, M S Sy 1
PMCID: PMC507379  PMID: 8675697

Abstract

Collagen-induced arthritis (CIA) in susceptible strains of mice is an animal model of T cell-mediated inflammatory polyarthritis. Analysis of T cell receptor (TCR) V beta gene usage in cells isolated from arthritic joints of BUB/BnJ (BUB) mice (H-2q, TCR V beta a) showed that TCR V beta chain gene usage was limited to TCR V beta 3 and V beta 10 gene families. All of the BUB mice immunized with a mixture of TCR V beta 3 and TCR V beta 10 peptides, but not with control TCR V beta 14 peptide, were refractory to the induction of CIA. Immunization with TCR V beta 3 and V beta 10 peptides completely blocked the development of clinical and subclinical inflammation, formation of pannus and synovial hyperplasia, and the erosion of cartilage and bone. Further studies revealed that preimmunization of BUB mice with V beta 10 peptide alone was sufficient to render the mice resistant to CIA. Analysis of TCR V beta chain gene expression in lymph node cells from arthritic and arthritis-protected mice showed the expression of TCR V beta 10 subfamily in all of the arthritic mice, but not in arthritis-protected mice. Immunization with TCR V beta peptides did not diminish the humoral responses to chicken type-II collagen and also elicited significant levels of anti-V beta 3 and anti-V beta 10 peptide antibodies. Antibodies cross-reactive with mouse chicken type-II collagen were detected in both the arthritic and arthritis-protected mice. Adoptive transfer of serum from arthritis-protected BUB mice significantly delayed the onset (P < 0.005) of arthritis in recipient BUB mice. In contrast, mice injected with serum from arthritic mice had early onset of arthritis. These results demonstrate that immunization of BUB mice with TCR V beta chain peptides elicited antibodies reactive with the self-TCR and prevented the induction of collagen-induced arthritis by eliminating or downregulating pathogenic T cells and consequently blocking the development of humoral immune response. These findings may have clinical applications in treating human autoimmune diseases characterized by common TCR gene usage.

Full Text

The Full Text of this article is available as a PDF (451.1 KB).

Selected References

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

  1. Acha-Orbea H., Mitchell D. J., Timmermann L., Wraith D. C., Tausch G. S., Waldor M. K., Zamvil S. S., McDevitt H. O., Steinman L. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell. 1988 Jul 15;54(2):263–273. doi: 10.1016/0092-8674(88)90558-2. [DOI] [PubMed] [Google Scholar]
  2. Banerjee S., Haqqi T. M., Luthra H. S., Stuart J. M., David C. S. Possible role of V beta T cell receptor genes in susceptibility to collagen-induced arthritis in mice. J Exp Med. 1988 Mar 1;167(3):832–839. doi: 10.1084/jem.167.3.832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broeren C. P., Lucassen M. A., van Stipdonk M. J., van der Zee R., Boog C. J., Kusters J. G., van Eden W. CDR1 T-cell receptor beta-chain peptide induces major histocompatibility complex class II-restricted T-T cell interactions. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5997–6001. doi: 10.1073/pnas.91.13.5997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Durie F. H., Fava R. A., Foy T. M., Aruffo A., Ledbetter J. A., Noelle R. J. Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40. Science. 1993 Sep 3;261(5126):1328–1330. doi: 10.1126/science.7689748. [DOI] [PubMed] [Google Scholar]
  5. Goss J. A., Alexander-Miller M. A., Gorka J., Flye M. W., Connolly J. M., Hansen T. H. Specific prolongation of allograft survival by a T-cell-receptor-derived peptide. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9872–9876. doi: 10.1073/pnas.90.21.9872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Haqqi T. M., Anderson G. D., Banerjee S., David C. S. Restricted heterogeneity in T-cell antigen receptor V beta gene usage in the lymph nodes and arthritic joints of mice. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1253–1255. doi: 10.1073/pnas.89.4.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Haqqi T. M., David C. S. T-cell receptor V beta genes repertoire in mice. Possible role in resistance and susceptibility to type II collagen-induced arthritis. J Autoimmun. 1990 Apr;3(2):113–121. doi: 10.1016/0896-8411(90)90135-f. [DOI] [PubMed] [Google Scholar]
  8. Haqqi T. M., Qu X. M., Sy M. S., Banerjee S. Restricted expression of T cell receptor V beta and lymphokine genes in arthritic joints of a TCR V beta a (H-2q) mouse strain-BUB/BnJ-with collagen-induced arthritis. Autoimmunity. 1995;20(3):163–170. doi: 10.3109/08916939508993347. [DOI] [PubMed] [Google Scholar]
  9. Holmdahl R., Andersson M., Goldschmidt T. J., Gustafsson K., Jansson L., Mo J. A. Type II collagen autoimmunity in animals and provocations leading to arthritis. Immunol Rev. 1990 Dec;118:193–232. doi: 10.1111/j.1600-065x.1990.tb00817.x. [DOI] [PubMed] [Google Scholar]
  10. Holmdahl R., Malmström V., Vuorio E. Autoimmune recognition of cartilage collagens. Ann Med. 1993 Jun;25(3):251–264. doi: 10.3109/07853899309147871. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Matsuoka N., Bernard N., Concepcion E. S., Graves P. N., Ben-Nun A., Davies T. F. T-cell receptor V region beta-chain gene expression in the autoimmune thyroiditis of non-obese diabetic mice. J Immunol. 1993 Aug 1;151(3):1691–1701. [PubMed] [Google Scholar]
  13. Myers L. K., Stuart J. M., Kang A. H. A CD4 cell is capable of transferring suppression of collagen-induced arthritis. J Immunol. 1989 Dec 15;143(12):3976–3980. [PubMed] [Google Scholar]
  14. Offner H., Hashim G. A., Vandenbark A. A. T cell receptor peptide therapy triggers autoregulation of experimental encephalomyelitis. Science. 1991 Jan 25;251(4992):430–432. doi: 10.1126/science.1989076. [DOI] [PubMed] [Google Scholar]
  15. Ortman R. A., Holderbaum D., Qu X. M., Banerjee S., Haqqi T. M. BUB/BnJ (H-2q) is a TCR deletion mutant mouse strain (TCR V beta a, KJ16-) that is susceptible to type II collagen-induced arthritis. J Immunol. 1994 Apr 15;152(8):4175–4182. [PubMed] [Google Scholar]
  16. Osman G. E., Toda M., Kanagawa O., Hood L. E. Characterization of the T cell receptor repertoire causing collagen arthritis in mice. J Exp Med. 1993 Feb 1;177(2):387–395. doi: 10.1084/jem.177.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Stuart J. M., Watson W. C., Kang A. H. Collagen autoimmunity and arthritis. FASEB J. 1988 Nov;2(14):2950–2956. doi: 10.1096/fasebj.2.14.3053308. [DOI] [PubMed] [Google Scholar]
  18. Urban J. L., Kumar V., Kono D. H., Gomez C., Horvath S. J., Clayton J., Ando D. G., Sercarz E. E., Hood L. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell. 1988 Aug 12;54(4):577–592. doi: 10.1016/0092-8674(88)90079-7. [DOI] [PubMed] [Google Scholar]
  19. Vandenbark A. A., Hashim G., Offner H. Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature. 1989 Oct 12;341(6242):541–544. doi: 10.1038/341541a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES