51. Soluble MHC-II proteins promote suppressive activity in CD4+ T cells.
- Author
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Bakela K, Kountourakis N, Aivaliotis M, and Athanassakis I
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing immunology, Animals, Antigens genetics, Antigens immunology, CD28 Antigens genetics, CD28 Antigens immunology, CD4-Positive T-Lymphocytes cytology, CTLA-4 Antigen genetics, CTLA-4 Antigen immunology, Histocompatibility Antigens Class II genetics, Histocompatibility Antigens Class II immunology, Humans, Immune Tolerance genetics, Interleukin-10 genetics, Interleukin-10 immunology, Interleukin-2 Receptor alpha Subunit genetics, Interleukin-2 Receptor alpha Subunit immunology, Membrane Proteins genetics, Membrane Proteins immunology, Mice, Mice, Inbred BALB C, Phosphoproteins genetics, Phosphoproteins immunology, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell immunology, Solubility, ZAP-70 Protein-Tyrosine Kinase genetics, ZAP-70 Protein-Tyrosine Kinase immunology, Antigens pharmacology, CD4-Positive T-Lymphocytes immunology, Histocompatibility Antigens Class II pharmacology, Immune Tolerance drug effects
- Abstract
Soluble MHCII (sMHCII) molecules are present in body fluids of healthy individuals and are considered to be involved in the maintenance of self tolerance, and are also related to various diseases. Their concentration increases during in vivo antigen-specific tolerogenic stimulation and it was recently shown that exosome-mediated tolerance is MHCII dependent. At the cellular level, sMHCII proteins compete with membrane MHCII for T-cell receptor binding on CD4(+) T cells. Immunoaffinity purification techniques isolated sMHCII antigens from the serum of human serum albumin (HSA) -tolerant mice as a single highly glycosylated protein of ~ 60,000 molecular weight, specifically interacting with anti-class II antibodies in Western blotting and ELISA. Mass spectroscopy showed that these sMHCII proteins were loaded with the tolerogenic peptide as well as multiple self peptides. At the cellular level, sMHCII suppressed antigen-specific, and to a lesser degree antigen-non-specific, spleen cell proliferation and induced CD25 in naive T cells. In T cells activated by antigen-seeded macrophages, sMHCII decreased CD28 and increased CTLA-4 protein expression, while decreasing interleukin-2 and increasing interleukin-10 production. In this case, sMHCII proteins were shown to decrease ZAP-70 and LAT phosphorylation. The results presented here for the first time provide evidence for the role of sMHCII proteins in immune response suppression and maintenance of tolerance, revealing novel regulatory mechanisms for immune system manipulation., (© 2014 John Wiley & Sons Ltd.) more...
- Published
- 2015
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