Abstract
Previous studies from our laboratory and those of others suggested the possibility that the T-cell antigen receptor alpha (TCR alpha) chain from some T cells can be released in a soluble form and can have antigen-specific immunoregulatory activity. We have analyzed this phenomenon by in vitro transcription and translation (IVTT) of a cDNA encoding a TCR alpha chain (A1.1 TCR alpha) suspected of having such activity. We found that TCR alpha, but not TCR beta, protein produced in this way showed antigen-specific regulatory activity in an in vitro immune-response assay. Protein derived from truncated forms of the A1.1 TCR alpha cDNA had activity providing that, in addition to the variable (V) and joining (J) regions of the alpha chain (VJ alpha), at least the first 25 amino acids of the alpha chain of the constant (C) region (C alpha) were present. Addition of an irrelevant protein sequence to the VJ alpha failed to impart activity to the molecule, suggesting that the C alpha requirement is not simply for stabilization of the resulting protein. These results are discussed in the context of other recent studies on the immunoregulatory activity of soluble TCR alpha molecules, and the possible physiological relevance of these observations is considered.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Asherson G. L., Colizzi V., Zembala M. An overview of T-suppressor cell circuits. Annu Rev Immunol. 1986;4:37–68. doi: 10.1146/annurev.iy.04.040186.000345. [DOI] [PubMed] [Google Scholar]
- Beaman K. D., Ruddle N. H., Bothwell A. L., Cone R. E. Messenger RNA for an antigen-specific binding molecule from an antigen-specific T-cell hybrid. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1524–1528. doi: 10.1073/pnas.81.5.1524. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bissonnette R., Zheng H. G., Kubo R. T., Singh B., Green D. R. A T helper cell hybridoma produces an antigen-specific regulatory activity. Relationship to the T cell receptor by serology and antigenic fine specificity. J Immunol. 1991 May 1;146(9):2898–2907. [PubMed] [Google Scholar]
- Bloom B. R., Modlin R. L., Salgame P. Stigma variations: observations on suppressor T cells and leprosy. Annu Rev Immunol. 1992;10:453–488. doi: 10.1146/annurev.iy.10.040192.002321. [DOI] [PubMed] [Google Scholar]
- Bonifacino J. S., Cosson P., Klausner R. D. Colocalized transmembrane determinants for ER degradation and subunit assembly explain the intracellular fate of TCR chains. Cell. 1990 Nov 2;63(3):503–513. doi: 10.1016/0092-8674(90)90447-m. [DOI] [PubMed] [Google Scholar]
- Bristow C. L., Flood P. M. T cell antigen receptor immune complexes demonstrating biologic and proteolytic activity. Int Immunol. 1993 Jan;5(1):79–88. doi: 10.1093/intimm/5.1.79. [DOI] [PubMed] [Google Scholar]
- 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]
- Dorf M. E., Kuchroo V. K., Collins M. Suppressor T cells: some answers but more questions. Immunol Today. 1992 Jul;13(7):241–243. doi: 10.1016/0167-5699(92)90002-O. [DOI] [PubMed] [Google Scholar]
- 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]
- Green D. R., Bissonnette R., Zheng H. G., Onda T., Echeverri F., Mogil R. J., Steele J. K., Voralia M., Fotedar A. Immunoregulatory activity of the T-cell receptor alpha chain demonstrated by retroviral gene transfer. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8475–8479. doi: 10.1073/pnas.88.19.8475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Green D. R., Zheng H. Antigen-specific regulatory T-cell factors and the T-cell receptor. Res Immunol. 1989 Mar-Apr;140(3):294–345. doi: 10.1016/0923-2494(89)90065-5. [DOI] [PubMed] [Google Scholar]
- Greenwood J., Willis A. E., Perham R. N. Multiple display of foreign peptides on a filamentous bacteriophage. Peptides from Plasmodium falciparum circumsporozoite protein as antigens. J Mol Biol. 1991 Aug 20;220(4):821–827. doi: 10.1016/0022-2836(91)90354-9. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Janeway C. A., Jr Do suppressor T cells exist? A reply. Scand J Immunol. 1988 Jun;27(6):621–623. doi: 10.1111/j.1365-3083.1988.tb02392.x. [DOI] [PubMed] [Google Scholar]
- Jorgensen J. L., Reay P. A., Ehrich E. W., Davis M. M. Molecular components of T-cell recognition. Annu Rev Immunol. 1992;10:835–873. doi: 10.1146/annurev.iy.10.040192.004155. [DOI] [PubMed] [Google Scholar]
- Kang A. S., Barbas C. F., Janda K. D., Benkovic S. J., Lerner R. A. Linkage of recognition and replication functions by assembling combinatorial antibody Fab libraries along phage surfaces. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4363–4366. doi: 10.1073/pnas.88.10.4363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Kuchroo V. K., Byrne M. C., Atsumi Y., Greenfield E., Connolly J. B., Whitters M. J., O'Hara R. M., Jr, Collins M., Dorf M. E. T-cell receptor alpha chain plays a critical role in antigen-specific suppressor cell function. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8700–8704. doi: 10.1073/pnas.88.19.8700. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Monroe J. G., Lowy A., Granstein R. D., Greene M. I. Studies of immune responsiveness and unresponsiveness to the p-azobenzenearsonate (ABA) hapten. Immunol Rev. 1984 Aug;80:103–131. doi: 10.1111/j.1600-065x.1984.tb00497.x. [DOI] [PubMed] [Google Scholar]
- Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
- Murphy D. B. T cell mediated immunosuppression. Curr Opin Immunol. 1993 Jun;5(3):411–417. doi: 10.1016/0952-7915(93)90061-v. [DOI] [PubMed] [Google Scholar]
- Möller G. Do suppressor T cells exist? Scand J Immunol. 1988 Mar;27(3):247–250. doi: 10.1111/j.1365-3083.1988.tb02344.x. [DOI] [PubMed] [Google Scholar]
- Ricciardi-Castagnoli P., Robbiati F., Barbanti E., Colizzi V., Pini C., De Santis R., Doria G., Adorini L. Immunosuppression by cell-free translation products from monoclonal antigen-specific suppressor T cell mRNA. Eur J Immunol. 1985 Apr;15(4):351–355. doi: 10.1002/eji.1830150409. [DOI] [PubMed] [Google Scholar]
- Shin J., Lee S., Strominger J. L. Translocation of TCR alpha chains into the lumen of the endoplasmic reticulum and their degradation. Science. 1993 Mar 26;259(5103):1901–1904. doi: 10.1126/science.8456316. [DOI] [PubMed] [Google Scholar]
- Taniguchi M., Tokuhisa T., Kanno M., Yaoita Y., Shimizu A., Honjo T. Reconstitution of antigen-specific suppressor activity with translation products of mRNA. Nature. 1982 Jul 8;298(5870):172–174. doi: 10.1038/298172a0. [DOI] [PubMed] [Google Scholar]
- Urbanski M., Cone R. E. Appearance of T lymphocyte-derived proteins specific for the immunizing antigen in serum during a humoral immune response. J Immunol. 1992 May 1;148(9):2840–2844. [PubMed] [Google Scholar]
- Wieder K. J., Araneo B. A., Kapp J. A., Webb D. R. Cell-free translation of a biologically active, antigen-specific suppressor T cell factor. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3599–3603. doi: 10.1073/pnas.79.11.3599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamaguchi K., Mori A., Ohno H., Tagaya Y., Ishizaka K. Requirement of certain epitope specificities of glycosylation inhibiting factor for the suppression of in vivo IgE and IgG antibody responses. Int Immunol. 1992 Mar;4(3):337–346. doi: 10.1093/intimm/4.3.337. [DOI] [PubMed] [Google Scholar]
- Zheng H., Boyer M., Fotedar A., Singh B., Green D. R. An antigen-specific helper T cell hybridoma produces an antigen-specific suppressor inducer molecule with identical antigenic fine specificity. Implications for the antigen recognition and function of helper and suppressor inducer T cells. J Immunol. 1988 Mar 1;140(5):1351–1358. [PubMed] [Google Scholar]
- 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]