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

Journal of Immunology

Volumn 180, Issue 12, 2008, Pages 8444-8454

  Greidinger, Eric L ^a,b   Zang, Yun Juan ^a   Jaimes, Kimberly ^a   Martinez, Laisel ^b   Nassiri, Mehdi ^a   Hoffman, Robert W ^a,b,c  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

^c UNIVERSITY OF MIAMI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIGEN; EPITOPE; HLA DR4 ANTIGEN; RNA BINDING PROTEIN; SMALL NUCLEAR RIBONUCLEOPROTEIN AUTOANTIGEN; T LYMPHOCYTE RECEPTOR; T LYMPHOCYTE RECEPTOR BETA CHAIN; UNCLASSIFIED DRUG; AUTOANTIBODY; HLA A ANTIGEN; HLA DR ANTIGEN; HLA DRB1*0101 ANTIGEN, HUMAN; HLA-DRB1 ANTIGEN; HLA-DRB1*0101 ANTIGEN, HUMAN; SMALL NUCLEAR RIBONUCLEOPROTEIN; SNRP70 PROTEIN, MOUSE;

AMINO ACID SEQUENCE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN PRESENTING CELL; ANTIGEN SPECIFICITY; ARTICLE; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; MIXED CONNECTIVE TISSUE DISEASE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; SEQUENCE ALIGNMENT; ANIMAL; BIOSYNTHESIS; C57BL MOUSE; CELL LINE; CELL MOTION; DISEASE MODEL; GENE REARRANGEMENT; GENETICS; HUMAN; IMMUNOLOGY; METABOLISM; MOLECULAR GENETICS; PATHOLOGY; PROTEIN TERTIARY STRUCTURE; TRANSGENIC MOUSE;

AMINO ACID SEQUENCE; ANIMALS; AUTOANTIBODIES; AUTOANTIGENS; CD4-POSITIVE T-LYMPHOCYTES; CELL LINE; CELL MOVEMENT; DISEASE MODELS, ANIMAL; EPITOPES, T-LYMPHOCYTE; GENE REARRANGEMENT, BETA-CHAIN T-CELL ANTIGEN RECEPTOR; HLA-A ANTIGENS; HLA-DR ANTIGENS; HLA-DR4 ANTIGEN; HUMANS; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MIXED CONNECTIVE TISSUE DISEASE; MOLECULAR SEQUENCE DATA; PROTEIN STRUCTURE, TERTIARY; RIBONUCLEOPROTEIN, U1 SMALL NUCLEAR; RIBONUCLEOPROTEINS, SMALL NUCLEAR;

EID: 50949132634     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.180.12.8444     Document Type: Article

References (39)

1. Holyst, M.-M., and R. W. Hoffman. 199S. U-small nuclear ribonucleoprolein (RNP)-reactive autoantibodies: diagnostic testing and clinical interpretation. Clin. Immunol. Newsl. 18: 53-55.
2. Hoffman, R. W. 2004. Overlap syndromes: mixed connective tissue disease and Sjögren's syndrome. In Systemic Lupus Erylhematosus, 4th Ed. R. G. Lahita, ed. Academic Press, New York, p. 717-744.
3. Hoffman, R. W. 2007. Mixed connective tissue disease and other connective tissue diseases. In Dubois Systemic Lupus Erythematosus, 7th Ed. D. J. Wallace and B. Hannahs Hahn, eds. New York, p. 975-991.
4. Burdt, M. A., R. W. Hoffman, S. L. Deutscher, G. S. Wang, J. C. Johnson, and G. C. Sharp. 1999. Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings. Arthritis Rheum. 42: 899-909.
5. Kramer, A. 1996. The structure and function of proteins involved in mammalian pre-mRNA splicing. Annu. Rev. Biochem. 65: 367-409.
6. Pettersson, I., M. Hinterberger, T. Mimori, E. Gottlieb, and J. A. Steitz. 1984. The structure of mammalian small nuclear ribonucleoproteins: identification of multiple protein components reactive with anti-(U1) ribonucleoprotein and anti-Sm autoantibodies. J. Biol. Chem. 259: 5907-5914.
7. Hinterberger, M., I. Pettersson, and J. A. Steitz. 1983. Isolation of small nuclear ribonucleoproteins containing Ul, U2, U4, U5, and U6 RNAs. J. Biol. Chem. 258: 2604-2613.
8. Query, C. C., R. C. Bentley, and J. D. Keene. 1989. A common RNA recognition motif identified within a defined Ul RNA binding domain of the 70K Ul snRNP protein. Cell 57: 89-101.
9. Kaneoka, H., K.-C. Hsu, Y. Takeda, G. C. Sharp, and R. W. Hoffman. 1992. Molecular genetic analysis of HLA-DR and HLA-DQ genes among anti-Ul-70-kd autoantibody positive connective tissue disease patients. Arthritis Rheum. 35: 83-94.
10. Cervino, A. C. L., N. F. Tsinoremas, and R. W. Hoffman. 2007. A genome-wide study of lupus: preliminary analysis and data release. Ann. NY Acad. Sci. 1110: 131-139.
11. Hoffman, R. W., Y. Takeda, G. C. Sharp, D. R. Lee, H. Kaneoka, and C. W. Caldwell. 1993. Human T cell clones reactive against U-small nuclear ribonucleoprotein autoantigens from connective tissue disease patients and healthy individuals. J. Immunol. 151: 6460-6469.
12. Holyst, M.-M., D. L. Hill, S. O. Hoch, and R. W. Hoffman. 1997. Analysis of human T cell and B cell responses against U small nuclear ribonucleoprotein 70-k, B and D polypeptides among patients with systemic lupus erythematosus and mixed connective tissue disease. Arthritis Rheum. 40: 1493-1503.
13. Greidinger, E. L., T. Gazitt, K. F. Jaimes, and R. W. Hoffman. 2004. Human T cell clones specific for heterogeneous nuclear ribonucleoprotein A2 autoantigen from connective tissue disease patients assist in autoantibody production. Arthritis Rheum. 50: 2216-2222.
14. Hoffman, R. W. 2004. T cells in the pathogenesis of systemic lupus erythematosus. Clin. Immunol. 113: 4-13.
15. Talken, B. L., D. R. Lee, C. W. Caldwell, T. P. Quinn, K. R. Schafermeyer, and R. W. Hoffman. 1999. Analysis of T cell receptors specific for Ul-70-kD small nuclear ribonucleoprotein autoantigen: the α chain complementarity determining region three is highly conserved among connective tissue disease patients. Hum. Immunol. 60: 200-208.
16. Talken, B. L., C W. Bailey, S. L. Reardon, C. W. Caldwell, and R. W. Hoffman. 2001. Structural analysis of TCR α and β chains from human T-cell clones specific for small nuclear ribonucleoprotein polypeptides Sm-D, Sm-B and Ul-70 kDa: TCR complementarity determining region 3 usage appears highly conserved. Scand. J. Immunol. 54: 204-210.
17. Greidinger, E. L., M. F. Foecking, K. R. Schäfermeyer, C. W. Bailey, S. L. Primm, D. R. Lee, and R. W. Hoffman. 2002. T cell immunity in connective tissue disease patients targets the RNA binding domain of the Ul-70-kD small nuclear ribonucleoprotein. J. Immunol. 169: 3429-3437.
18. Ito, K., H.-H. Brian, M. Molina, J. Han, J. Magram, E. Saar, C. Belunis, D. R. Bolin, R. Arceo, R. Campbell, et al. 1996. HLA-DR4-IE chimeric class II transgenic, murine class H-deficient mice are susceptible to experimental allergic encephalitis. J. Exp. Med. 183: 2635-2644.
19. Greidinger, E. L., M. F. Foecking, J. Magee, L. Wilson, S. Ranatunga, R. A. Ortmann, and R. W. Hoffman. 2004. A major B cell epitope present on the apoptotic but not the intact form of the U1-70-kDa ribonucleoprotein autoantigen. J. Immunol. 172: 709-716.
20. Greidinger, E. L., Y. Zang, K. Jaimes, S. Hogenmiller, M. Nassiri, P. Bejarano, G. N. Barber, and R. W. Hoffman. 2006. A murine model of mixed connective tissue disease induced with Ul small nuclear RNP autoantigen. Arthritis Rheum. 54: 661-669.
21. Greidinger, E. L., and R. W. Hoffman. 2001. The appearance of U1 RNP antibody specificities in sequential autoimmune human antisera follows a characteristic order that implicates the Ul-70 kd and B7B proteins as predominant Ul RNP immunogens. Arthritis Rheum. 44: 368-375.
22. Hoffman, R. W., G. C. Sharp, and S. L. Deutscher. 1995. Analysis of anti-U1 RNA antibodies in patients with connective tissue disease: association with HLA and clinical manifestations of disease. Arthritis Rheum. 38: 1837-1844.
23. McMurray, R. W., R. W. Hoffman, H. Tang, and H. Braley-Mullen. 1996. T cell receptor Vβ usage in murine experimental autoimmune thyroiditis. Cell. Immunol. 172: 1-9.
24. Cornberg, M., A. T. Chen, L. A. Wilkinson, M. A. Brchm, S. K. Kim, C. Calcagno, D. Ghersi, R. Puzone, F. Celada, R. M. Welsh, and L. K. Selin. 2006. Narrowed TCR repertoire and viral escape as a consequence of heterolo-gous immunity. J. Clin. Invest. 116: 1443-1456.
25. + T-cell immune response. Immunol. Rev. 172: 335-343.
26. *0401) transgenic mice are encephalitogenic and are presented by human B cells. J. Immunol. 167:7119-7125.
27. Madsen, L. S., E. C. Andersson, L. Jansson, M. Krogsgaard, C. B. Andersen, J. Engberg, J. L. Strominger, A. Svejgaard, J. P. Hjorth, R. Holmdahl, et al. 1999. A humanized model for multiple sclerosis using HLA-DR2 and a human T-cell receptor. Nat. Genet. 23: 343-347.
28. *0201. Arthritis Rheum. 56: 3387-3398.
29. + T cells reactive with Ul-70-kD autoantigen can transfer disease and are central to pathogenesis in new murinc model of lupus. Clin. Immunol. 123: S83 (Abstract).
30. Monneaux, F., and S. Muller. 2001. Key sequences involved in spreading of the systemic autoimmune response to spliceosome proteins. Scand. J. Immunol. 54: 45-54.
31. Mamula, M. J., S. Fatenejad, and J. Craft. 1994. B cells process and present lupus autoantigens that initiate autoimmune T cell responses. J. Immunol. 152: 1453-1461.
32. Monneaux, F., V. Pariette, J.-P. Briand, and S. Muller. 2004. Intramolecular T cell spreading in unprimed MRL/lpr mice. Arthritis Rheum. 50: 3232-3228.
33. + T cells from lupus patients by a promiscuous, protective peptide analogue. J. Immunol. 175: 5839-5847.
34. Talken, B. L., K. R. Schäfermeyer, C. W. Bailey, D. R. Lee, and R. W. Hoffman. 2001. T cell epitope mapping of the Smith autoantigen reveals that highly conserved Smith antigen motifs are the dominant target of T cell immunity in systemic lupus erythematosus. J. Immunol. 167: 562-568.
35. Talken, B. L., M.-M. Holyst, D. R. Lee, and R. W. Hoffman. 1999. T cell receptor β-chain third complementarity-determining region gene usage is highly restricted among Sm-B autoantigen-specific human T cell clones derived from patients with connective tissue disease. Arthritis Rheum. 42: 703-709.
36. Davies, T. F., A. Martin, E. S. Concepscion, P. Graves, L. Cohen, and A. Ben-Nun. 1991. Evidence for limited variability of antigen receptors on in-trathyroidal T cells in autoimmune thyroid disease. N. Engl. J. Med. 325: 238-244.
37. + intestinal mucosa T cells in ulcerative colitis. J. Immunol. 156: 3024-3035.
38. Mantegazza, R., F. Andreetta, P. Bemasconi, F. Baggi, J. R. Oksenberg, O. Simoncini, M. Mora, F. Comelio, and L. Steinman. 1993. Analysis of T cell receptor repertoire of muscle-infiltrating T lymphocytes in polymyositis. J. Clin. Invest. 91: 2880-2886.
39. Hoffman, R. W. 2006. T-cell directed therapy in systemic lupus erythematosus. Future Rheumatol. 1: 597-605.