Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Oct 1;88(19):8700–8704. doi: 10.1073/pnas.88.19.8700

T-cell receptor alpha chain plays a critical role in antigen-specific suppressor cell function.

V K Kuchroo 1, M C Byrne 1, Y Atsumi 1, E Greenfield 1, J B Connolly 1, M J Whitters 1, R M O'Hara Jr 1, M Collins 1, M E Dorf 1
PMCID: PMC52577  PMID: 1833764

Abstract

Antigen-specific suppressor T-cell hybridomas release soluble suppressor factors (TsF) in the supernatant that modulate both in vivo delayed-type hypersensitivity and in vitro plaque-forming cell responses in an antigen-specific manner. To study the relationship between the T-cell receptor (TcR) and TsF, we developed a series of TcR alpha- or TcR beta- expression variants from suppressor T-cell hybridomas that expressed the CD3-TcR alpha/beta complex. We demonstrate that loss of TcR alpha but not TcR beta mRNA was accompanied by the concomitant loss of suppressor bioactivity. Homologous transfection of TcR alpha cDNA into a TcR alpha- beta+ clone reconstituted both CD3-TcR expression and suppressor function. Furthermore, suppressor activity from TcR beta- variants was specifically absorbed by antigen and anti-TcR alpha antibodies, but not by anti-CD3 or anti-TcR beta affinity columns. These data directly establish a role for the TcR alpha chain in suppressor T-cell function and suggest that the TcR alpha chain is part of the antigen-specific TsF molecule.

Full text

PDF
8700

Images in this article

8701Image
on p.8701
8701Image
on p.8701

Selected References

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

  1. Bonifacino J. S., Suzuki C. K., Klausner R. D. A peptide sequence confers retention and rapid degradation in the endoplasmic reticulum. Science. 1990 Jan 5;247(4938):79–82. doi: 10.1126/science.2294595. [DOI] [PubMed] [Google Scholar]
  2. Chien Y., Becker D. M., Lindsten T., Okamura M., Cohen D. I., Davis M. M. A third type of murine T-cell receptor gene. Nature. 1984 Nov 1;312(5989):31–35. doi: 10.1038/312031a0. [DOI] [PubMed] [Google Scholar]
  3. Cohen I. R. Regulation of autoimmune disease physiological and therapeutic. Immunol Rev. 1986 Dec;94:5–21. doi: 10.1111/j.1600-065x.1986.tb01161.x. [DOI] [PubMed] [Google Scholar]
  4. Collins M., Kuchroo V. K., Whitters M. J., O'Hara R. M., Jr, Kelleher K., Kubo R. T., Dorf M. E. Expression of functional alpha beta T cell receptor gene rearrangements in suppressor T cell hybridomas correlates with antigen binding, but not with suppressor cell function. J Immunol. 1990 Nov 1;145(9):2809–2819. [PubMed] [Google Scholar]
  5. De Santis R., Givol D., Hsu P. L., Adorini L., Doria G., Appella E. Rearrangement and expression of the alpha- and beta-chain genes of the T-cell antigen receptor in functional murine suppressor T-cell clones. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8638–8642. doi: 10.1073/pnas.82.24.8638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dorf M. E., Benacerraf B. Suppressor cells and immunoregulation. Annu Rev Immunol. 1984;2:127–157. doi: 10.1146/annurev.iy.02.040184.001015. [DOI] [PubMed] [Google Scholar]
  7. Fairchild R. L., Kubo R. T., Moorhead J. W. DNP-specific/class I MHC-restricted suppressor molecules bear determinants of the T cell receptor alpha- and beta-chains. The V beta 8+ chain dictates restriction to either K or D. J Immunol. 1990 Oct 1;145(7):2001–2009. [PubMed] [Google Scholar]
  8. Fairchild R. L., Kubo R. T., Moorhead J. W. Soluble factors in tolerance and contact sensitivity to 2,4-dinitro-fluorobenzene in mice. IX. A monoclonal T cell suppressor molecule is structurally and serologically related to the alpha/beta T cell receptor. J Immunol. 1988 Nov 15;141(10):3342–3348. [PubMed] [Google Scholar]
  9. Hausman P. B., Sherr D. H., Dorf M. E. An in vitro system for the generation of suppressor cells and the requirement for B cells in their induction. J Immunol. 1985 Mar;134(3):1388–1396. [PubMed] [Google Scholar]
  10. Hedrick S. M., Germain R. N., Bevan M. J., Dorf M., Engel I., Fink P., Gascoigne N., Heber-Katz E., Kapp J., Kaufmann Y. Rearrangement and transcription of a T-cell receptor beta-chain gene in different T-cell subsets. Proc Natl Acad Sci U S A. 1985 Jan;82(2):531–535. doi: 10.1073/pnas.82.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Imai K., Kanno M., Kimoto H., Shigemoto K., Yamamoto S., Taniguchi M. Sequence and expression of transcripts of the T-cell antigen receptor alpha-chain gene in a functional, antigen-specific suppressor-T-cell hybridoma. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8708–8712. doi: 10.1073/pnas.83.22.8708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Iwata M., Katamura K., Kubo R. T., Grey H. M., Ishizaka K. Relationship between T cell receptors and antigen-binding factors. II. Common antigenic determinants and epitope recognition shared by T cell receptors and antigen-binding factors. J Immunol. 1989 Dec 15;143(12):3917–3924. [PubMed] [Google Scholar]
  13. Iwata M., Katamura K., Kubo R. T., Ishizaka K. Relationship between T cell receptors and antigen-binding factors. I. Specificity of functional T cell receptors on mouse T cell hybridomas that produce antigen-binding T cell factors. J Immunol. 1989 Dec 15;143(12):3909–3916. [PubMed] [Google Scholar]
  14. Jayaraman S., Bellone C. J. Hapten-specific responses to the phenyltrimethylamino hapten. V. A single chain antigen-binding I-J+ first-order T suppressor factor requires antigen to induce anti-idiotypic second-order suppressor T cells. J Immunol. 1985 Feb;134(2):1010–1018. [PubMed] [Google Scholar]
  15. Kishi H., Borgulya P., Scott B., Karjalainen K., Traunecker A., Kaufman J., von Boehmer H. Surface expression of the beta T cell receptor (TCR) chain in the absence of other TCR or CD3 proteins on immature T cells. EMBO J. 1991 Jan;10(1):93–100. doi: 10.1002/j.1460-2075.1991.tb07924.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kronenberg M., Goverman J., Haars R., Malissen M., Kraig E., Phillips L., Delovitch T., Suciu-Foca N., Hood L. Rearrangement and transcription of the beta-chain genes of the T-cell antigen receptor in different types of murine lymphocytes. Nature. 1985 Feb 21;313(6004):647–653. doi: 10.1038/313647a0. [DOI] [PubMed] [Google Scholar]
  17. Kuchroo V. K., Steele J. K., Billings P. R., Selvaraj P., Dorf M. E. Expression of CD3-associated antigen-binding receptors on suppressor T cells. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9209–9213. doi: 10.1073/pnas.85.23.9209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kuchroo V. K., Steele J. K., O'Hara R. M., Jr, Jayaraman S., Selvaraj P., Greenfield E., Kubo R. T., Dorf M. E. Relationships between antigen-specific helper and inducer suppressor T cell hybridomas. J Immunol. 1990 Jul 15;145(2):438–448. [PubMed] [Google Scholar]
  19. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  20. Salgame P., Convit J., Bloom B. R. Immunological suppression by human CD8+ T cells is receptor dependent and HLA-DQ restricted. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2598–2602. doi: 10.1073/pnas.88.6.2598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Seed B. An LFA-3 cDNA encodes a phospholipid-linked membrane protein homologous to its receptor CD2. 1987 Oct 29-Nov 4Nature. 329(6142):840–842. doi: 10.1038/329840a0. [DOI] [PubMed] [Google Scholar]
  22. Sorensen C. M., Pierce C. W. Monoclonal antibodies specific for single chain or two chain GAT-specific suppressor factors: production and analysis of in vitro modulating properties. J Immunol. 1985 Jul;135(1):362–367. [PubMed] [Google Scholar]
  23. Takata M., Maiti P. K., Kubo R. T., Chen Y. H., Holford-Strevens V., Rector E. S., Sehon A. H. Cloned suppressor T cells derived from mice tolerized with conjugates of antigen and monomethoxypolyethylene glycol. Relationship between monoclonal T suppressor factor and the T cell receptor. J Immunol. 1990 Nov 1;145(9):2846–2853. [PubMed] [Google Scholar]
  24. Tan K. N., Datlof B. M., Gilmore J. A., Kronman A. C., Lee J. H., Maxam A. M., Rao A. The T cell receptor V alpha 3 gene segment is associated with reactivity to p-azobenzenearsonate. Cell. 1988 Jul 15;54(2):247–261. doi: 10.1016/0092-8674(88)90557-0. [DOI] [PubMed] [Google Scholar]
  25. Weiner D. B., Liu J., Hanna N., Bluestone J. A., Coligan J. E., Williams W. V., Greene M. I. CD3-associated heterodimeric polypeptides on suppressor hybridomas define biologically active inhibitory cells. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6077–6081. doi: 10.1073/pnas.85.16.6077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wileman T., Carson G. R., Shih F. F., Concino M. F., Terhorst C. The transmembrane anchor of the T-cell antigen receptor beta chain contains a structural determinant of pre-Golgi proteolysis. Cell Regul. 1990 Nov;1(12):907–919. doi: 10.1091/mbc.1.12.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wilson S. D., Burd P. R., Billings P. R., Martin C. A., Dorf M. E. The expression and regulation of a potential lymphokine gene (TCA3) in CD4 and CD8 T cell clones. J Immunol. 1988 Sep 1;141(5):1563–1570. [PubMed] [Google Scholar]
  28. Zheng H., Sahai B. M., Kilgannon P., Fotedar A., Green D. R. Specific inhibition of cell-surface T-cell receptor expression by antisense oligodeoxynucleotides and its effect on the production of an antigen-specific regulatory T-cell factor. Proc Natl Acad Sci U S A. 1989 May;86(10):3758–3762. doi: 10.1073/pnas.86.10.3758. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES