Abstract
We have analyzed cytokine gene expression by a murine CD4+ T-cell clone that expresses three forms of T-cell recognition. The clone employs a V beta 6-containing T-cell receptor to recognize (i) a self class II major histocompatibility complex and an ovalbumin-derived peptide (OVA), (ii) an I-Ab alloantigen, and (iii) Mls-1a. All three responses are accompanied by similar levels of cell proliferation. However, although interferon gamma gene expression is strongly induced during both physiological recognition of the OVA peptide and allogeneic major histocompatibility complex recognition, expression of this gene was not detected during the Mls response. These studies indicate that Mls recognition is functionally distinct from T-cell recognition of peptides and alloantigens and leads to an alternative pattern of cytokine gene expression. They also suggest the possibility that encounter with these two classes of T-cell antigen in vivo may generate subsets of T helper cells that display different patterns of cytokine gene expression.
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- Abbasi K., Festenstein H. Antigenic strength investigated by cell-mediated lympholysis in mice. Eur J Immunol. 1973 Jul;3(7):430–435. doi: 10.1002/eji.1830030711. [DOI] [PubMed] [Google Scholar]
- Abromson-Leeman S. R., Cantor H. Specificity of T cell clones for antigen and autologous major histocompatibility complex products determines specificity for foreign major histocompatibility complex products. J Exp Med. 1983 Aug 1;158(2):428–437. doi: 10.1084/jem.158.2.428. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Abromson-Leeman S. R., Der Simonian H., Clabby M., Cantor H. Analysis of insulin-specific T cell clones. I. Strategy for production of clonotypic antibody. J Immunol. 1986 May 1;136(9):3184–3188. [PubMed] [Google Scholar]
- Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
- Buus S., Sette A., Grey H. M. The interaction between protein-derived immunogenic peptides and Ia. Immunol Rev. 1987 Aug;98:115–141. doi: 10.1111/j.1600-065x.1987.tb00522.x. [DOI] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Dellabona P., Peccoud J., Kappler J., Marrack P., Benoist C., Mathis D. Superantigens interact with MHC class II molecules outside of the antigen groove. Cell. 1990 Sep 21;62(6):1115–1121. doi: 10.1016/0092-8674(90)90388-u. [DOI] [PubMed] [Google Scholar]
- Friedman S., Sillcocks D., Cantor H. Alloreactivity of an OVA-specific T-cell clone. I. Stimulation by class II MHC and novel non-MHC B-cell determinants. Immunogenetics. 1987;26(4-5):193–203. doi: 10.1007/BF00346512. [DOI] [PubMed] [Google Scholar]
- Friedman S., Sillcocks D., Rao A., Faas S., Cantor H. A subset of Ly-1 inducer T cell clones activates B cell proliferation but directly inhibits subsequent IgG secretion. J Exp Med. 1985 Apr 1;161(4):785–804. doi: 10.1084/jem.161.4.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hünig T., Bevan M. J. Specificity of T-cell cones illustrates altered self hypothesis. Nature. 1981 Dec 3;294(5840):460–462. doi: 10.1038/294460a0. [DOI] [PubMed] [Google Scholar]
- Janeway C. A., Jr, Yagi J., Conrad P. J., Katz M. E., Jones B., Vroegop S., Buxser S. T-cell responses to Mls and to bacterial proteins that mimic its behavior. Immunol Rev. 1989 Feb;107:61–88. doi: 10.1111/j.1600-065x.1989.tb00003.x. [DOI] [PubMed] [Google Scholar]
- Janeway C. A. The Mls locus: past, present and future. J Immunogenet. 1988 Feb-Jun;15(1-3):1–4. doi: 10.1111/j.1744-313x.1988.tb00401.x. [DOI] [PubMed] [Google Scholar]
- Kappler J. W., Staerz U., White J., Marrack P. C. Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature. 1988 Mar 3;332(6159):35–40. doi: 10.1038/332035a0. [DOI] [PubMed] [Google Scholar]
- Kashima N., Nishi-Takaoka C., Fujita T., Taki S., Yamada G., Hamuro J., Taniguchi T. Unique structure of murine interleukin-2 as deduced from cloned cDNAs. 1985 Jan 31-Feb 6Nature. 313(6001):402–404. doi: 10.1038/313402a0. [DOI] [PubMed] [Google Scholar]
- Katz M. E., Janeway C. A., Jr The immunobiology of T cell responses to Mls-locus-disparate stimulator cells. II. Effects of Mls-locus-disparate stimulator cells on cloned, protein antigen-specific, Ia-restricted T cell lines. J Immunol. 1985 Apr;134(4):2064–2070. [PubMed] [Google Scholar]
- Korngold R., Sprent J. Surface markers of T cells causing lethal graft-vs-host disease to class I vs class II H-2 differences. J Immunol. 1985 Nov;135(5):3004–3010. [PubMed] [Google Scholar]
- MacDonald H. R., Schneider R., Lees R. K., Howe R. C., Acha-Orbea H., Festenstein H., Zinkernagel R. M., Hengartner H. T-cell receptor V beta use predicts reactivity and tolerance to Mlsa-encoded antigens. Nature. 1988 Mar 3;332(6159):40–45. doi: 10.1038/332040a0. [DOI] [PubMed] [Google Scholar]
- Matis L. A., Sorger S. B., McElligott D. L., Fink P. J., Hedrick S. M. The molecular basis of alloreactivity in antigen-specific, major histocompatibility complex-restricted T cell clones. Cell. 1987 Oct 9;51(1):59–69. doi: 10.1016/0092-8674(87)90010-9. [DOI] [PubMed] [Google Scholar]
- Miller R. A., Stutman O. Enumeration of IL 2-secreting helper T cells by limiting dilution analysis, and demonstration of unexpectedly high levels of IL 2 production per responding cell. J Immunol. 1982 May;128(5):2258–2264. [PubMed] [Google Scholar]
- Mond J. J., Finkelman F. D., Sarma C., Ohara J., Serrate S. Recombinant interferon-gamma inhibits the B cell proliferative response stimulated by soluble but not by Sepharose-bound anti-immunoglobulin antibody. J Immunol. 1985 Oct;135(4):2513–2517. [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]
- O'Rourke A. M., Mescher M. F., Webb S. R. Activation of polyphosphoinositide hydrolysis in T cells by H-2 alloantigen but not MLS determinants. Science. 1990 Jul 13;249(4965):171–174. doi: 10.1126/science.2164711. [DOI] [PubMed] [Google Scholar]
- Patarca R., Freeman G. J., Schwartz J., Singh R. P., Kong Q. T., Murphy E., Anderson Y., Sheng F. Y., Singh P., Johnson K. A. rpt-1, an intracellular protein from helper/inducer T cells that regulates gene expression of interleukin 2 receptor and human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2733–2737. doi: 10.1073/pnas.85.8.2733. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patarca R., Freeman G. J., Singh R. P., Wei F. Y., Durfee T., Blattner F., Regnier D. C., Kozak C. A., Mock B. A., Morse H. C., 3rd Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection. J Exp Med. 1989 Jul 1;170(1):145–161. doi: 10.1084/jem.170.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Payne J., Huber B. T., Cannon N. A., Schneider R., Schilham M. W., Acha-Orbea H., MacDonald H. R., Hengartner H. Two monoclonal rat antibodies with specificity for the beta-chain variable region V beta 6 of the murine T-cell receptor. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7695–7698. doi: 10.1073/pnas.85.20.7695. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Piechaczyk M., Blanchard J. M., Marty L., Dani C., Panabieres F., El Sabouty S., Fort P., Jeanteur P. Post-transcriptional regulation of glyceraldehyde-3-phosphate-dehydrogenase gene expression in rat tissues. Nucleic Acids Res. 1984 Sep 25;12(18):6951–6963. doi: 10.1093/nar/12.18.6951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pullen A. M., Kappler J. W., Marrack P. Tolerance to self antigens shapes the T-cell repertoire. Immunol Rev. 1989 Feb;107:125–139. doi: 10.1111/j.1600-065x.1989.tb00006.x. [DOI] [PubMed] [Google Scholar]
- Rabin E. M., Mond J. J., Ohara J., Paul W. E. Interferon-gamma inhibits the action of B cell stimulatory factor (BSF)-1 on resting B cells. J Immunol. 1986 Sep 1;137(5):1573–1576. [PubMed] [Google Scholar]
- Reynolds D. S., Boom W. H., Abbas A. K. Inhibition of B lymphocyte activation by interferon-gamma. J Immunol. 1987 Aug 1;139(3):767–773. [PubMed] [Google Scholar]
- Webb S. R., Molnar-Kimber K., Bruce J., Sprent J., Wilson D. B. T cell clones with dual specificity for M1s and various major histocompatibility complex determinants. J Exp Med. 1981 Dec 1;154(6):1970–1974. doi: 10.1084/jem.154.6.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]