Abstract
A secreted product of a T cell leukemic cell line, LH-8, was examined for its biochemical and biological properties. The factor that we have termed Immunoglobulin-Binding T cell Suppressor Factor (IgB-TsF) was shown to be suppressive for the in vitro and in vivo humoral response to a variety (but not all) antigens tested. The cell surface phenotype of the LH-8.1 subclone was M.Ig(-), Thy-1(+), L3T4(-), Lyt-2(+), FcR(- ), MAC-1(-), and H-2b(+). In addition, both the cell surface and secreted factor, IgB-TsF, of LH-8.1 expressed determinants that were recognized by anti-I-Jb mAbs but not by an anti-I-Jd monoclonal. The same factor also retained an affinity for the Fc portion of approximately 30% of randomly selected, purified mAbs. This binding could be abolished if the Fab or F(ab')2 fragments of these mAb were used, but was found to be unrelated to isotype of the respective mAbs. Using subclones that expressed quantitative differences in their ability to exert suppression as sources of biosynthetically labeled IgB- TsF, we have shown the suppressor activity correlated with a single, 28 kD protein. Furthermore, comparisons of these same subclones that differ in their suppressor activity, do not show any direct correlation of this biological activity with the expression of the previously described T cell receptor genes. It also suggests that at least some suppressor cell subsets may use the same or related family of T cell receptor genes for their recognitive stage of activation as helper and cytotoxic T cell subsets, but not for their effector stage of immunologic suppression.
Full Text
The Full Text of this article is available as a PDF (1.2 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adorini L., Doria G., Ricciardi-Castagnoli P. Fine antigenic specificity and genetic restriction of lysozyme-specific suppressor T cell factor produced by radiation leukemia virus-transformed suppressor T cells. Eur J Immunol. 1982 Sep;12(9):719–724. doi: 10.1002/eji.1830120905. [DOI] [PubMed] [Google Scholar]
- Ahmad-Zadeh C., Piguet J. D., Colli L. Molecular weight estimation of immunoglobulin subunits of polyacrylamide gel. Immunology. 1971 Dec;21(6):1065–1071. [PMC free article] [PubMed] [Google Scholar]
- Allison J. P., McIntyre B. W., Bloch D. Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol. 1982 Nov;129(5):2293–2300. [PubMed] [Google Scholar]
- Andersson J., Buxbaum J., Citronbaum R., Douglas S., Forni L., Melchers F., Pernis B., Stott D. IgM-producing tumors in the BALB-c mouse: a model for B-cell maturation. J Exp Med. 1974 Sep 1;140(3):742–763. doi: 10.1084/jem.140.3.742. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Casey J., Davidson N. Rates of formation and thermal stabilities of RNA:DNA and DNA:DNA duplexes at high concentrations of formamide. Nucleic Acids Res. 1977;4(5):1539–1552. doi: 10.1093/nar/4.5.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cianciolo G. J., Lostrom M. E., Tam M., Snyderman R. Murine malignant cells synthesize a 19,000-dalton protein that is physicochemically and antigenically related to the immunosuppressive retroviral protein, P15E. J Exp Med. 1983 Sep 1;158(3):885–900. doi: 10.1084/jem.158.3.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Fridman W. H., Guimezanes A., Gisler R. H. Characterization of suppressive immunoglobulin-binding factor (IBF). I. Production of IBF by a theta-positive lymphoma (L-5178-Y). J Immunol. 1977 Oct;119(4):1266–1268. [PubMed] [Google Scholar]
- Fridman W. H., Rabourdin-Combe C., Neauport-Sautes C., Gisler R. H. Characterization and function of T cell Fc gamma receptor. Immunol Rev. 1981;56:51–88. doi: 10.1111/j.1600-065x.1981.tb01047.x. [DOI] [PubMed] [Google Scholar]
- Gershon R. K. T cell control of antibody production. Contemp Top Immunobiol. 1974;3:1–40. doi: 10.1007/978-1-4684-3045-5_1. [DOI] [PubMed] [Google Scholar]
- Glimcher L. H., Hamano T., Asofsky R., Herber-Katz E., Hedrick S., Schwartz R. H., Paul W. E. I region-restricted antigen presentation by B cell-B lymphoma hybridomas. Nature. 1982 Jul 15;298(5871):283–284. doi: 10.1038/298283a0. [DOI] [PubMed] [Google Scholar]
- Goding J. W. Conjugation of antibodies with fluorochromes: modifications to the standard methods. J Immunol Methods. 1976;13(3-4):215–226. doi: 10.1016/0022-1759(76)90068-5. [DOI] [PubMed] [Google Scholar]
- Golub E. S., Mishell R. I., Weigle W. O., Dutton R. W. A modification of the hemolytic plaque assay for use with protein antigens. J Immunol. 1968 Jan;100(1):133–137. [PubMed] [Google Scholar]
- Hayes C. E., Klyczek K. K., Krum D. P., Whitcomb R. M., Hullett D. A., Cantor H. Chromosome 4 Jt gene controls murine T cell surface I-J expression. Science. 1984 Feb 10;223(4636):559–563. doi: 10.1126/science.6607530. [DOI] [PubMed] [Google Scholar]
- Hedrick S. M., Cohen D. I., Nielsen E. A., Davis M. M. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984 Mar 8;308(5955):149–153. doi: 10.1038/308149a0. [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]
- Jerne N. K., Nordin A. A. Plaque Formation in Agar by Single Antibody-Producing Cells. Science. 1963 Apr 26;140(3565):405–405. doi: 10.1126/science.140.3565.405. [DOI] [PubMed] [Google Scholar]
- Kappler J., Kubo R., Haskins K., Hannum C., Marrack P., Pigeon M., McIntyre B., Allison J., Trowbridge I. The major histocompatibility complex-restricted antigen receptor on T cells in mouse and man: identification of constant and variable peptides. Cell. 1983 Nov;35(1):295–302. doi: 10.1016/0092-8674(83)90232-5. [DOI] [PubMed] [Google Scholar]
- Krupen K., Araneo B. A., Brink L., Kapp J. A., Stein S., Wieder K. J., Webb D. R. Purification and characterization of a monoclonal T-cell suppressor factor specific for poly(LGlu60LAla30LTyr10). Proc Natl Acad Sci U S A. 1982 Feb;79(4):1254–1258. doi: 10.1073/pnas.79.4.1254. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lynch R. G., Rohrer J. W., Odermatt B., Gebel H. M., Autry J. R., Hoover R. G. Immunoregulation of murine myeloma cell growth and differentiation: a monoclonal model of B cell differentiation. Immunol Rev. 1979;48:45–80. doi: 10.1111/j.1600-065x.1979.tb00298.x. [DOI] [PubMed] [Google Scholar]
- Löwy I., Brezin C., Neauport-Sautes C., Theze J., Fridman W. H. Isotype regulation of antibody production: T-cell hybrids can be selectively induced to produce IgG1 and IgG2 subclass-specific suppressive immunoglobulin-binding factors. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2323–2327. doi: 10.1073/pnas.80.8.2323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marshak-Rothstein A., Siekevitz M., Margolies M. N., Mudgett-Hunter M., Gefter M. L. Hybridoma proteins expressing the predominant idiotype of the antiazophenylarsonate response of A/J mice. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1120–1124. doi: 10.1073/pnas.77.2.1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McMaster G. K., Carmichael G. G. Analysis of single- and double-stranded nucleic acids on polyacrylamide and agarose gels by using glyoxal and acridine orange. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4835–4838. doi: 10.1073/pnas.74.11.4835. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Minami M., Okuda K., Furusawa S., Benacerraf B., Dorf M. E. Analysis of T cell hybridomas. I. Characterization of H-2 and Igh-restricted monoclonal suppressor factors. J Exp Med. 1981 Nov 1;154(5):1390–1402. doi: 10.1084/jem.154.5.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy D. B., Horowitz M. C., Homer R. J., Flood P. M. Genetic, serological and functional analysis of I-J molecules. Immunol Rev. 1985 Apr;83:79–103. doi: 10.1111/j.1600-065x.1985.tb00471.x. [DOI] [PubMed] [Google Scholar]
- Norcross M. A., Smith R. T., Shimizu S. Regulation of TCGF production in T cells. II. Early membrane events after anti-Thy-1 binding by the TCGF-producing T lymphoma EL-4 G-12. J Immunol. 1984 Feb;132(2):833–838. [PubMed] [Google Scholar]
- Okuda K., Minami M., Ju S. T., Dorf M. E. Functional association of idiotypic and I-J determinants on the antigen receptor of suppressor T cells. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4557–4561. doi: 10.1073/pnas.78.7.4557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orosz C. G., Zinn N. E., Olsen R. G., Mathes L. E. Retrovirus-mediated immunosuppression. II. FeLV-UV alters in vitro murine T lymphocyte behavior by reversibly impairing lymphokine secretion. J Immunol. 1985 Jul;135(1):583–590. [PubMed] [Google Scholar]
- Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
- Reinherz E. L., Acuto O., Fabbi M., Bensussan A., Milanese C., Royer H. D., Meuer S. C., Schlossman S. F. Clonotypic surface structure on human T lymphocytes: functional and biochemical analysis of the antigen receptor complex. Immunol Rev. 1984 Oct;81:95–129. doi: 10.1111/j.1600-065x.1984.tb01106.x. [DOI] [PubMed] [Google Scholar]
- Ricciardi-Castagnoli P., Doria G., Adorini L. Production of antigen-specific suppressive T cell factor by radiation leukemia virus-transformed suppressor T cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3804–3808. doi: 10.1073/pnas.78.6.3804. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. 1984 Jun 28-Jul 4Nature. 309(5971):757–762. doi: 10.1038/309757a0. [DOI] [PubMed] [Google Scholar]
- Saito T., Taniguchi M. Chemical features of an antigen-specific suppressor T cell factor composed of two polypeptide chains. J Mol Cell Immunol. 1984;1(3):137–145. [PubMed] [Google Scholar]
- Samelson L. E., Schwartz R. H. Characterization of the antigen-specific T cell receptor from a pigeon cytochrome c-specific T cell hybrid. Immunol Rev. 1984 Oct;81:131–144. doi: 10.1111/j.1600-065x.1984.tb01107.x. [DOI] [PubMed] [Google Scholar]
- Tada T., Uracz W., Abe R., Asano Y. I-J as an inducible T cell receptor for self. Immunol Rev. 1985 Apr;83:105–124. doi: 10.1111/j.1600-065x.1985.tb00472.x. [DOI] [PubMed] [Google Scholar]
- Taniguchi M., Hayakawa K., Tada T. Properties of antigen-specific suppressive T cell factor in the regulation of antibody response of the mouse. II. In vitro activity and evidence for the I region gene product. J Immunol. 1976 Feb;116(2):542–548. [PubMed] [Google Scholar]
- Thèze J., Waltenbaugh C., Dorf M. E., Benacerraf B. Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyrosine50 (GT) II. Presence of I-J determinants on the GT-suppressive factor. J Exp Med. 1977 Jul 1;146(1):287–292. doi: 10.1084/jem.146.1.287. [DOI] [PMC free article] [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]