Abstract
Delayed type hypersensitivity to the hapten azobenzenearsonate (ABA) can be induced and suppressed by the administration of hapten-coupled syngeneic spleen cells by the appropriate route. Suppressor T cells stimulated by the intravenous administration of ABA-coupled spleen cells have been shown to produce a discrete subcellular factor(s) which is capable of suppressing delayed type hypersensitivity to azobenzenearsonate in the mouse. Such suppressor factors may be produced by the mechanical disruption of suppressor cells or by placing such suppressor cells in culture for 24 h. The suppressor factor(s) (SF) derived from ABA-specific suppressor cells exhibit biological specificity for the suppression of ABA delayed type hypersensitivity (DTH), but not trinitro-phenyl DTH, as well as the capacity to bind to ABA immunoadsorbents. Passage of suppressor factor(s) over reverse immunoadsorbents utilizing a rabbit anti-mouse F(ab')2 antiserum demonstrated that the antigen-specific T-cell derived SF does not bear conventional immunoglobulin markers. The suppressor factor(s) are not immunoglobulin molecules was further demonstrated by the inability of anti-ABA antibodies to suppress ABA DTH. Gel filtration of ABA suppressor factor(s) showed that the majority of the suppressive activity was present in a fraction with molecular weight ranging between 6.8 x 10(4) and 3.3 x 10(4) daltons. We also analyzed for the presence of determinants encoded by the H-2 major histocompatibility complex (MHC) and found that immunoadsorbents prepared utilizing antisera capable of interacting with gene products of the whole or selected gene regions of H-2 MHC, i.e., B10.D2 anti-B10.A and B10 anti- B10.A immunoadsorbents, retained the suppressive activity of ABA-SF. Elution of such columns with glycine HCl buffers (pH 2.8) permitted recovery of specific suppressive activity. Taken collectively such data supports the notion that suppressor T-cell-derived ABA suppressor factors have antigen-binding specificity as well as determinants controlled by the K end of the H-2 MHC. The distribution of strains capable of making SF has also been analyzed. The relationship of the antigen-binding specificity to VH gene products is discussed in this and the companion paper.
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Selected References
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- Asherson G. L., Zembala M. Suppressor T cells in cell-mediated immunity. Br Med Bull. 1976 May;32(2):158–164. doi: 10.1093/oxfordjournals.bmb.a071349. [DOI] [PubMed] [Google Scholar]
- Bach B. A., Sherman L., Benacerraf B., Greene M. I. Mechanisms of regulation of cell-mediated immunity. II. Induction and suppression of delayed-type hypersensitivity to azobenzenearsonate-coupled syngeneic cells. J Immunol. 1978 Oct;121(4):1460–1468. [PubMed] [Google Scholar]
- Battisto J. R., Bloom B. R. Dual immunological unresponsiveness induced by cell membrane coupled hapten or antigen. Nature. 1966 Oct 8;212(5058):156–157. doi: 10.1038/212156a0. [DOI] [PubMed] [Google Scholar]
- Binz H., Wigzell H., Bazin H. T-cell idiotypes are linked to immunoglobulin heavy chain genes. Nature. 1976 Dec 16;264(5587):639–642. doi: 10.1038/264639a0. [DOI] [PubMed] [Google Scholar]
- Cosenza H., Julius M. H., Augustin A. A. Idiotypes as variable region markers: analogies between receptors on phosphorylcholine-specific T and B lymphocytes. Immunol Rev. 1977;34:3–33. doi: 10.1111/j.1600-065x.1977.tb00366.x. [DOI] [PubMed] [Google Scholar]
- Cuatrecasas P. Protein purification by affinity chromatography. Derivatizations of agarose and polyacrylamide beads. J Biol Chem. 1970 Jun;245(12):3059–3065. [PubMed] [Google Scholar]
- Germain R. N., Thèze J., Kapp J. A., Benacerraf B. Antigen-specific T-cell-mediated suppression. I. Induction of L-glutamic acid60-L-alanine30-L-tyrosine10 specific suppressor T cells in vitro requires both antigen-specific T-cell-suppressor factor and antigen. J Exp Med. 1978 Jan 1;147(1):123–136. doi: 10.1084/jem.147.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gershon R. K., Kondo K. Infectious immunological tolerance. Immunology. 1971 Dec;21(6):903–914. [PMC free article] [PubMed] [Google Scholar]
- Greene M. I., Fujimoto S., Sehon A. H. Regulation of the immune response to tumor antigens. III. Characterization of thymic suppressor factor(s) produced by tumor-bearing hosts. J Immunol. 1977 Aug;119(2):757–764. [PubMed] [Google Scholar]
- Greene M. I., Pierres A., Dorf M. E., Benacerraf B. The I-J subregion codes for determinats on suppressor factor(s) which limit the contact sensitivity response to picryl chloride. J Exp Med. 1977 Jul 1;146(1):293–296. doi: 10.1084/jem.146.1.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greene M. I., Sugimoto M., Benacerraf B. Mechanisms of regulation of cell-mediated immune responses. I. Effect of the route of immunization with TNP-coupled syngeneic cells on the induction and suppression of contact sensitivity to picryl chloride. J Immunol. 1978 May;120(5):1604–1611. [PubMed] [Google Scholar]
- Jack R. S., Imanishi-Kari T., Rajewsky K. Idiotypic analysis of the response of C57BL/6 mice to the (4-hydroxy-3-nitrophenyl)acetyl group. Eur J Immunol. 1977 Aug;7(8):559–565. doi: 10.1002/eji.1830070813. [DOI] [PubMed] [Google Scholar]
- Ju S. T., Sato S., Nisonoff A. Transfer of idiotype suppression and idiotypes by leukocytes from ascitic fluids. Eur J Immunol. 1977 Jun;7(6):401–405. doi: 10.1002/eji.1830070614. [DOI] [PubMed] [Google Scholar]
- Kapp J. A., Pierce C. W., Benacerraf B. Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) II. Cellular source and effect on responder and nonresponder mice. J Exp Med. 1977 Apr 1;145(4):828–838. doi: 10.1084/jem.145.4.828. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kontiainen S., Feldmann M. Suppressor-cell induction in vitro. IV. Target of antigen-specific suppressor factor and its genetic relationships. J Exp Med. 1978 Jan 1;147(1):110–122. doi: 10.1084/jem.147.1.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krammer P. H., Eichmann K. T cell receptor idiotypes are controlled by genes in the heavy chain linkage group and the major histocompatibility complex. Nature. 1977 Dec 22;270(5639):733–735. doi: 10.1038/270733a0. [DOI] [PubMed] [Google Scholar]
- Kuettner M. G., Wang A. L., Nisonoff A. Quantitative investigations of idiotypic antibodies. VI. Idiotypic specificity as a potential genetic marker for the variable regions of mouse immunoglobulin polypeptide chains. J Exp Med. 1972 Mar 1;135(3):579–595. doi: 10.1084/jem.135.3.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laskin J. A., Gray A., Nisonoff A., Klinman N. R., Gottlieb P. D. Segregation at a locus determining an immunoglobulin genetic marker for the light chain variable region affects inheritance of expression of an idiotype. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4600–4604. doi: 10.1073/pnas.74.10.4600. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewis G. K., Goodman J. W. Purification of functional, determinant-specific, idiotype-bearing murine T cells. J Exp Med. 1978 Oct 1;148(4):915–924. doi: 10.1084/jem.148.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller S. D., Claman H. N. The induction of hapten-specific T cell tolerance by using hapten-modified lymphoid cells. I. Characteristics of tolerance induction. J Immunol. 1976 Nov;117(5 Pt 1):1519–1526. [PubMed] [Google Scholar]
- Nisonoff A., Ju S. T., Owen F. L. Studies of structure and immunosuppression of cross-reactive idiotype in strain A mice. Immunol Rev. 1977;34:89–118. doi: 10.1111/j.1600-065x.1977.tb00369.x. [DOI] [PubMed] [Google Scholar]
- Nisonoff A., Ju S. Studies of a cross-reactive idiotype associated with anti-para-azophenylarsonate antibodies of A/J mice. Ann Immunol (Paris) 1976 Jun-Jul;127(3-4):347–356. [PubMed] [Google Scholar]
- Pawlak L. L., Mushinski E. B., Nisonoff A., Potter M. Evidence for the linkage of the IGC H locus to a gene controlling the idiotypic specificity of anti-p-azophenylarsonate antibodies in strain A mice. J Exp Med. 1973 Jan 1;137(1):22–31. doi: 10.1084/jem.137.1.22. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pawlak L. L., Nisonoff A. Distribution of a cross-reactive idiotypic specificity in inbred strains of mice. J Exp Med. 1973 Apr 1;137(4):855–869. doi: 10.1084/jem.137.4.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perry L. L., Benacerraf B., Greene M. I. Regulation of the immune response to tumor antigen. IV. Tumor antigen-specific suppressor factor(s) bear I-J determinants and induce suppressor T cells in vivo. J Immunol. 1978 Dec;121(6):2144–2147. [PubMed] [Google Scholar]
- REIF A. E., ALLEN J. M. THE AKR THYMIC ANTIGEN AND ITS DISTRIBUTION IN LEUKEMIAS AND NERVOUS TISSUES. J Exp Med. 1964 Sep 1;120:413–433. doi: 10.1084/jem.120.3.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tada T., Taniguchi M., David C. S. Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex. J Exp Med. 1976 Sep 1;144(3):713–725. doi: 10.1084/jem.144.3.713. [DOI] [PMC free article] [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]
- Tung A. S., Nisonoff A. Isolation from individual A/J mice of anti-rho-azophenylarsonate antibodies bearing a cross-reactive idiotype. J Exp Med. 1975 Jan 1;141(1):112–126. doi: 10.1084/jem.141.1.112. [DOI] [PMC free article] [PubMed] [Google Scholar]