T cell immunity in connective tissue disease patients targets the RNA binding domain of the U1-70kDa small nuclear ribonucleoprotein

The Journal of Immunology : Official Journal of the American Association of Immunologists
Eric L GreidingerRobert W Hoffman

Abstract

Although the T cell dependence of autoimmune responses in connective tissue diseases has been well established, limited information exists regarding the T cell targeting of self Ags in humans. To characterize the T cell response to a connective tissue disease-associated autoantigen, this study generated T cell clones from patients using a set of peptides encompassing the entire linear sequence of the 70-kDa subunit of U1 snRNP (U1-70kDa) small nuclear ribonucleoprotein. Despite the ability of U1-70kDa to undergo multiple forms of Ag modification that have been correlated with distinct clinical disease phenotypes, a remarkably limited and consistent pattern of T cell targeting of U1-70kDa was observed. All tested T cell clones generated against U1-70kDa were specific for epitopes within the RNA binding domain (RBD) of the protein. High avidity binding of the RBD with U1-RNA was preserved with the disease-associated modified forms of U1-70kDa tested. The high avidity interaction between the U1-RBD on the polypeptide and U1-RNA may be critical in immune targeting of this region in autoimmunity. The T cell autoimmune response to U1-70kDa appears to have less diversity than is seen in the humoral response; and therefore, may be a fa...Continue Reading

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Jul 13, 2002·Arthritis and Rheumatism·Eric L GreidingerRobert W Hoffman

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Citations

Oct 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fanny MonneauxSylviane Muller
Jan 31, 2009·Arthritis and Rheumatism·Eric L GreidingerRobert W Hoffman
Mar 29, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·YunJuan ZangEric L Greidinger
Jan 29, 2016·HLA : Immune Response Genetics·A Paradowska-GoryckaM Jurkowska
Oct 1, 2004·Arthritis and Rheumatism·Robert W HoffmanEric L Greidinger
Mar 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mihiri De Silva-UdawattaRobert W Hoffman
Feb 7, 2003·Arthritis and Rheumatism·Robert W Hoffman, Eric L Greidinger
Sep 10, 2003·Current Opinion in Rheumatology·George C TsokosYuang-Taung Juang
Dec 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eric L GreidingerRobert W Hoffman
Feb 16, 2008·Journal of Autoimmune Diseases·Masha Fridkis-Hareli
Apr 29, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Robert W Hoffman, Marcos E Maldonado
Dec 25, 2009·Journal of Autoimmunity·Markus H HoffmannGünter Steiner

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