Abstract
Nearly one-third of IgM antilymphocyte autoantibody-positive sera from patients with systemic lupus erythematosus (SLE) contain IgM antibodies to one or more 180-220-kD molecules (p180, p190, p205, and p220) in blots of glycoproteins purified from T cells by wheat germ agglutinin affinity chromatography. Identity of these IgM targets with multiple isoforms of CD45 was established by their specific depletion from T cell glycoproteins by immunoprecipitation with T191, a monoclonal antibody (mAb) that reacts with an epitope common to all CD45 isoforms. Although the anti-CD45 autoantibodies recognize higher molecular weight isoforms primarily, antigenic specificity in this system is quite heterogeneous and includes multiple distinct CD45 isoforms on different types of T cells that are, at least in part, different from those reactive with mAbs 2H4 and UCHL-1. Because CD45 is a major membrane protein tyrosine phosphatase that plays a critical role in antigen- induced T cell activation, the present data may be relevant to some of the antilymphocyte antibody-mediated immunologic abnormalities that characterize SLE and related autoimmune diseases.
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Selected References
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- Clark E. A., Ledbetter J. A. Leukocyte cell surface enzymology: CD45 (LCA, T200) is a protein tyrosine phosphatase. Immunol Today. 1989 Jul;10(7):225–228. doi: 10.1016/0167-5699(89)90257-0. [DOI] [PubMed] [Google Scholar]
- Gottlieb A. B., Lahita R. G., Chiorazzi N., Kunkel H. G. Immune function in systemic lupus erythematosus. Impairment of in vitro T-cell proliferation and in vivo antibody response to exogenous antigen. J Clin Invest. 1979 May;63(5):885–892. doi: 10.1172/JCI109388. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ledbetter J. A., Rose L. M., Spooner C. E., Beatty P. G., Martin P. J., Clark E. A. Antibodies to common leukocyte antigen p220 influence human T cell proliferation by modifying IL 2 receptor expression. J Immunol. 1985 Sep;135(3):1819–1825. [PubMed] [Google Scholar]
- Ledbetter J. A., Tonks N. K., Fischer E. H., Clark E. A. CD45 regulates signal transduction and lymphocyte activation by specific association with receptor molecules on T or B cells. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8628–8632. doi: 10.1073/pnas.85.22.8628. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Minota S., Koyasu S., Yahara I., Winfield J. Autoantibodies to the heat-shock protein hsp90 in systemic lupus erythematosus. J Clin Invest. 1988 Jan;81(1):106–109. doi: 10.1172/JCI113280. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mittler R. S., Greenfield R. S., Schacter B. Z., Richard N. F., Hoffmann M. K. Antibodies to the common leukocyte antigen (T200) inhibit an early phase in the activation of resting human B cells. J Immunol. 1987 May 15;138(10):3159–3166. [PubMed] [Google Scholar]
- Morimoto C., Hafler D. A., Weiner H. L., Letvin N. L., Hagan M., Daley J., Schlossman S. F. Selective loss of the suppressor-inducer T-cell subset in progressive multiple sclerosis. Analysis with anti-2H4 monoclonal antibody. N Engl J Med. 1987 Jan 8;316(2):67–72. doi: 10.1056/NEJM198701083160202. [DOI] [PubMed] [Google Scholar]
- Morimoto C., Schlossman S. F. Antilymphocyte antibodies and systemic lupus erythematosus. Arthritis Rheum. 1987 Feb;30(2):225–228. doi: 10.1002/art.1780300215. [DOI] [PubMed] [Google Scholar]
- Morimoto C., Steinberg A. D., Letvin N. L., Hagan M., Takeuchi T., Daley J., Levine H., Schlossman S. F. A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody. J Clin Invest. 1987 Mar;79(3):762–768. doi: 10.1172/JCI112882. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mustelin T., Coggeshall K. M., Altman A. Rapid activation of the T-cell tyrosine protein kinase pp56lck by the CD45 phosphotyrosine phosphatase. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6302–6306. doi: 10.1073/pnas.86.16.6302. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pingel J. T., Thomas M. L. Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation. Cell. 1989 Sep 22;58(6):1055–1065. doi: 10.1016/0092-8674(89)90504-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenthal C. J., Franklin E. C. Depression of cellular-mediated immunity in systemic lupus erythematosus. relation to disease activity. Arthritis Rheum. 1975 May-Jun;18(3):207–217. doi: 10.1002/art.1780180303. [DOI] [PubMed] [Google Scholar]
- Schraven B., Roux M., Hutmacher B., Meuer S. C. Triggering of the alternative pathway of human T cell activation involves members of the T 200 family of glycoproteins. Eur J Immunol. 1989 Feb;19(2):397–403. doi: 10.1002/eji.1830190226. [DOI] [PubMed] [Google Scholar]
- Streuli M., Morimoto C., Schrieber M., Schlossman S. F., Saito H. Characterization of CD45 and CD45R monoclonal antibodies using transfected mouse cell lines that express individual human leukocyte common antigens. J Immunol. 1988 Dec 1;141(11):3910–3914. [PubMed] [Google Scholar]
- Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
- Tanaka S., Matsuyama T., Steinberg A. D., Schlossman S. F., Morimoto C. Antilymphocyte antibodies against CD4+2H4+ cell populations in patients with systemic lupus erythematosus. Arthritis Rheum. 1989 Apr;32(4):398–405. doi: 10.1002/anr.1780320408. [DOI] [PubMed] [Google Scholar]
- Terry L. A., Brown M. H., Beverley P. C. The monoclonal antibody, UCHL1, recognizes a 180,000 MW component of the human leucocyte-common antigen, CD45. Immunology. 1988 Jun;64(2):331–336. [PMC free article] [PubMed] [Google Scholar]
- Thomas M. L. The leukocyte common antigen family. Annu Rev Immunol. 1989;7:339–369. doi: 10.1146/annurev.iy.07.040189.002011. [DOI] [PubMed] [Google Scholar]
- Tonks N. K., Charbonneau H., Diltz C. D., Fischer E. H., Walsh K. A. Demonstration that the leukocyte common antigen CD45 is a protein tyrosine phosphatase. Biochemistry. 1988 Nov 29;27(24):8695–8701. doi: 10.1021/bi00424a001. [DOI] [PubMed] [Google Scholar]
- Winfield J. B., Shaw M., Yamada A., Minota S. Subset specificity of antilymhocyte antibodies in systemic lupus erythematosus. II. Preferential reactivity with T4 + cells is associated with relative depletion of autologous T4 + cells. Arthritis Rheum. 1987 Feb;30(2):162–168. doi: 10.1002/art.1780300206. [DOI] [PubMed] [Google Scholar]
- Yamada A., Cohen P. L., Winfield J. B. Subset specificity of antilymphocyte antibodies in systemic lupus erythematosus. Preferential reactivity with cells bearing the T4 and autologous erythrocyte receptor phenotypes. Arthritis Rheum. 1985 Mar;28(3):262–270. doi: 10.1002/art.1780280305. [DOI] [PubMed] [Google Scholar]
- Yamada A., Winfield J. B. Inhibition of soluble antigen-induced T cell proliferation by warm-reactive antibodies to activated T cells in systemic lupus erythematosus. J Clin Invest. 1984 Dec;74(6):1948–1960. doi: 10.1172/JCI111615. [DOI] [PMC free article] [PubMed] [Google Scholar]
