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

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.

• Authors: Eric L Greidinger, Mark F Foecking, Kim R Schäfermeyer, Craig W Bailey, Shannon L Primm, David R Lee, Robert W Hoffman
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 169 Issue 6 Pg. 3429-37 (Sep 15 2002) ISSN: 0022-1767 [Print] United States
• PMID: 12218166 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epitopes, T-Lymphocyte
• HLA-DR Antigens
• HLA-DRB1 Chains
• Peptide Fragments
• RNA, Small Nuclear
• RNA-Binding Proteins
• Ribonucleoprotein, U1 Small Nuclear
• SNRNP70 protein, human
• U1 small nuclear RNA
• Alanine

Topics

• Alanine (genetics)
• Amino Acid Sequence
• Blood Donors
• Clone Cells
• Connective Tissue Diseases (genetics, immunology)
• Epitopes, T-Lymphocyte (genetics, immunology)
• HLA-DR Antigens (genetics)
• HLA-DRB1 Chains
• Histocompatibility Testing
• Humans
• Molecular Sequence Data
• Mutagenesis, Site-Directed
• Peptide Fragments (genetics, immunology, metabolism)
• Peptide Mapping
• Protein Binding (immunology)
• Protein Structure, Tertiary (genetics)
• RNA, Small Nuclear (immunology)
• RNA-Binding Proteins (genetics, immunology, metabolism)
• Ribonucleoprotein, U1 Small Nuclear (genetics, immunology, metabolism)
• Sequence Homology, Amino Acid
• T-Lymphocyte Subsets (immunology)