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

Eric L. Greidinger, Mark F. Foecking, Kim R. Schäfermeyer, Craig W. Bailey, Shannon L. Primm, David R. Lee, Robert W. Hoffman

Research output: Contribution to journalArticle

35 Scopus citations

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 favorable target for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)3429-3437
Number of pages9
JournalJournal of Immunology
Volume169
Issue number6
DOIs
StatePublished - Sep 15 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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