HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

CD4+ T cells target epitopes residing within the RNA-binding domain of the U1-70-kDa small nuclear ribonucleoprotein autoantigen and have restricted TCR diversity in an HLA-DR4-transgenic murine model of mixed connective tissue disease.

Abstract
Mixed connective tissue disease (MCTD) is a systemic autoimmune disease with significant morbidity and premature mortality of unknown pathogenesis. In the present study, we characterized U1-70-kDa small nuclear ribonucleoprotein (70-kDa) autoantigen-specific T cells in a new murine model of MCTD. These studies defined 70-kDa-reactive T cell Ag fine specificities and TCR gene usage in this model. Similar to patients with MCTD, CD4(+) T cells can be readily identified from 70-kDa/U1-RNA-immunized HLA-DR4-transgenic mice. Using both freshly isolated CD4(+) T cells from spleen and lung, and T cell lines, we found that the majority of these T cells were directed against antigenic peptides residing within the RNA-binding domain of 70 kDa. We also found that TCR-beta (TRB) V usage was highly restricted among 70-kDa-reactive T cells, which selectively used TRBV subgroups 1, 2, 6, 8.1, 8.2, and 8.3, and that the TRB CDR3 had conserved sequence motifs which were shared across different TRBV subgroups. Finally, we found that the TRBV and CDR3 regions used by both murine and human 70-kDa-specific CD4(+) T cells were homologous. Thus, T cell recognition of the 70-kDa autoantigen by HLA-DR4-transgenic mice is focused on a limited number of T cell epitopes residing primarily within the RBD of the molecule, using a restricted number of TRBV and CDR3 motifs that are homologous to T cells isolated from MCTD patients.
AuthorsEric L Greidinger, Yun Juan Zang, Kimberly Jaimes, Laisel Martinez, Mehdi Nassiri, Robert W Hoffman
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 12 Pg. 8444-54 (Jun 15 2008) ISSN: 0022-1767 [Print] United States
PMID18523312 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Autoantibodies
  • Autoantigens
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-DR Antigens
  • HLA-DR4 Antigen
  • HLA-DRB1 Chains
  • HLA-DRB1*01:01 antigen
  • Ribonucleoprotein, U1 Small Nuclear
  • Ribonucleoproteins, Small Nuclear
  • Snrnp70 protein, mouse
Topics
  • Amino Acid Sequence
  • Animals
  • Autoantibodies (biosynthesis)
  • Autoantigens (administration & dosage, immunology, metabolism)
  • CD4-Positive T-Lymphocytes (immunology, metabolism, pathology)
  • Cell Line
  • Cell Movement (genetics, immunology)
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte (genetics, immunology, metabolism)
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • HLA-A Antigens (administration & dosage, genetics, immunology)
  • HLA-DR Antigens (administration & dosage, genetics, immunology)
  • HLA-DR4 Antigen (genetics)
  • HLA-DRB1 Chains
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mixed Connective Tissue Disease (genetics, immunology, pathology)
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Ribonucleoprotein, U1 Small Nuclear (administration & dosage, immunology, metabolism)
  • Ribonucleoproteins, Small Nuclear (administration & dosage, immunology, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: