| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,§,§
,§,§
*
Department of Molecular Immunology, Merck Research Laboratories, Rahway, NJ 07065; Departments of
Medicine and
Pediatrics, University of Tennessee, Memphis, TN 38163; and
§
Veterans Affairs Medical Center, Memphis, TN 38104
Although associations between the expression of particular HLA genes and the susceptibility to specific autoimmune diseases has been known for some time, the role that these HLA molecules play in the autoimmune response is unclear. Through the establishment of a chimeric HLA-DR/I-E transgene, we have examined the function of the rheumatoid arthritis (RA) susceptibility allele HLA-DR4 (DRB1*0401) in presenting antigenic peptides derived from the model Ag, type II collagen (CII), and in mediating an autoimmune response. As a transgene, the chimeric DR4 molecule conferred susceptibility to an autoimmune arthritis induced by immunization with human CII or bovine CII. These mice developed an inflammatory, autoimmune arthritis that was similar both histologically and in severity to that previously described for the collagen-induced arthritis model. The DR4-mediated autoimmune arthritis was accompanied by T cell and B cell responses to both the immunogen and the autoantigen, murine CII. The DR4-restricted T cell response to human CII was focused on an immunodominant determinant within CII263–270 and a minor determinant within CII286–300, the same CII determinants recently identified for yet another RA susceptibility allele, HLA-DR1 (DRB1*0101). Thus these data demonstrate that, like HLA-DR1, HLA-DR4 is capable of binding peptides derived from human CII and therefore probably plays a role in the autoimmune response to human CII observed in RA patients.
This article has been cited by other articles:
|
|
 |
|
  J. Huan, L. J. Kaler, J. L. Mooney, S. Subramanian, C. Hopke, A. A. Vandenbark, E. F. Rosloniec, G. G. Burrows, and H. Offner MHC Class II Derived Recombinant T Cell Receptor Ligands Protect DBA/1LacJ Mice from Collagen-Induced Arthritis J. Immunol., January 15, 2008; 180(2): 1249 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. von Delwig, D. M Altmann, F. G Charlton, N. McKie, J. D Isaacs, R. Holmdahl, and J. H Robinson T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice Ann Rheum Dis, May 1, 2007; 66(5): 599 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. F. Rosloniec, R. A. Ivey III, K. B. Whittington, A. H. Kang, and H.-W. Park Crystallographic Structure of a Rheumatoid Arthritis MHC Susceptibility Allele, HLA-DR1 (DRB1*0101), Complexed with the Immunodominant Determinant of Human Type II Collagen J. Immunol., September 15, 2006; 177(6): 3884 - 3892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Dzhambazov, K. S. Nandakumar, J. Kihlberg, L. Fugger, R. Holmdahl, and M. Vestberg Therapeutic Vaccination of Active Arthritis with a Glycosylated Collagen Type II Peptide in Complex with MHC Class II Molecules J. Immunol., February 1, 2006; 176(3): 1525 - 1533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Latham, K. B. Whittington, R. Zhou, Z. Qian, and E. F. Rosloniec Ex Vivo Characterization of the Autoimmune T Cell Response in the HLA-DR1 Mouse Model of Collagen-Induced Arthritis Reveals Long-Term Activation of Type II Collagen-Specific Cells and Their Presence in Arthritic Joints J. Immunol., April 1, 2005; 174(7): 3978 - 3985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Marin-Esteban, K. Falk, and O. Rotzschke "Chemical Analogues" of HLA-DM Can Induce a Peptide-receptive State in HLA-DR Molecules J. Biol. Chem., December 3, 2004; 279(49): 50684 - 50690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Cremer, X. J. Ye, L. K. Myers, D. D. Brand, E. F. Rosloniec, and A. H. Kang T Cell Immunity to Type II Collagen in the Biobreeding Rat: The Identification and Characterization of RT1u-Restricted T Cell Epitopes on {alpha}1(II) J. Immunol., August 1, 2004; 173(3): 1795 - 1801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Holmdahl, A. Grubb, and R. Holmdahl Cysteine proteases in Langerhans cells limits presentation of cartilage derived type II collagen for autoreactive T cells Int. Immunol., May 1, 2004; 16(5): 717 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Taylor, E. Havari, M. F. McInerney, R. Bronson, K. W. Wucherpfennig, and M. A. Lipes A Spontaneous Model for Autoimmune Myocarditis Using the Human MHC Molecule HLA-DQ8 J. Immunol., February 15, 2004; 172(4): 2651 - 2658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Backlund, K. S. Nandakumar, R. Bockermann, L. Mori, and R. Holmdahl Genetic Control of Tolerance to Type II Collagen and Development of Arthritis in an Autologous Collagen-Induced Arthritis Model J. Immunol., October 1, 2003; 171(7): 3493 - 3499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Vandenbark, C. Rich, J. Mooney, A. Zamora, C. Wang, J. Huan, L. Fugger, H. Offner, R. Jones, and G. G. Burrows Recombinant TCR Ligand Induces Tolerance to Myelin Oligodendrocyte Glycoprotein 35-55 Peptide and Reverses Clinical and Histological Signs of Chronic Experimental Autoimmune Encephalomyelitis in HLA-DR2 Transgenic Mice J. Immunol., July 1, 2003; 171(1): 127 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Cope Exploring the reciprocal relationship between immunity and inflammation in chronic inflammatory arthritis Rheumatology, June 1, 2003; 42(6): 716 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Tsark, W. Wang, Y.-C. Teng, D. Arkfeld, G. R. Dodge, and S. Kovats Differential MHC Class II-Mediated Presentation of Rheumatoid Arthritis Autoantigens by Human Dendritic Cells and Macrophages J. Immunol., December 1, 2002; 169(11): 6625 - 6633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Belmares, R. Busch, K. W. Wucherpfennig, H. M. McConnell, and E. D. Mellins Structural Factors Contributing to DM Susceptibility of MHC Class II/Peptide Complexes J. Immunol., November 1, 2002; 169(9): 5109 - 5117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Backlund, S. Carlsen, T. Hoger, B. Holm, L. Fugger, J. Kihlberg, H. Burkhardt, and R. Holmdahl Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis PNAS, July 23, 2002; 99(15): 9960 - 9965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. F. Rosloniec, K. B. Whittington, D. M. Zaller, and A. H. Kang HLA-DR1 (DRB1*0101) and DR4 (DRB1*0401) Use the Same Anchor Residues for Binding an Immunodominant Peptide Derived from Human Type II Collagen J. Immunol., January 1, 2002; 168(1): 253 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Brand, L. K. Myers, K. B. Whittington, K. A. Latham, J. M. Stuart, A. H. Kang, and E. F. Rosloniec Detection of Early Changes in Autoimmune T Cell Phenotype and Function Following Intravenous Administration of Type II Collagen in a TCR-Transgenic Model J. Immunol., January 1, 2002; 168(1): 490 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Corrigall, M. D. Bodman-Smith, M. S. Fife, B. Canas, L. K. Myers, P. H. Wooley, C. Soh, N. A. Staines, D. J. C. Pappin, S. E. Berlo, et al. The Human Endoplasmic Reticulum Molecular Chaperone BiP Is an Autoantigen for Rheumatoid Arthritis and Prevents the Induction of Experimental Arthritis J. Immunol., February 1, 2001; 166(3): 1492 - 1498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Phelps, V. Jones, A. N. Turner, and A. J. Rees Properties of HLA class II molecules divergently associated with Goodpasture's disease Int. Immunol., August 1, 2000; 12(8): 1135 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Touloukian, W. W. Leitner, S. L. Topalian, Y. F. Li, P. F. Robbins, S. A. Rosenberg, and N. P. Restifo Identification of a MHC Class II-Restricted Human gp100 Epitope Using DR4-IE Transgenic Mice J. Immunol., April 1, 2000; 164(7): 3535 - 3542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Kotzin, M. T. Falta, F. Crawford, E. F. Rosloniec, J. Bill, P. Marrack, and J. Kappler Use of soluble peptide-DR4 tetramers to detect synovial T cells specific for cartilage antigens in patients with rheumatoid arthritis PNAS, January 4, 2000; 97(1): 291 - 296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-T. Yang, J. Jirholt, L. Svensson, M. Sundvall, L. Jansson, U. Pettersson, and R. Holmdahl Identification of Genes Controlling Collagen-Induced Arthritis in Mice: Striking Homology with Susceptibility Loci Previously Identified in the Rat J. Immunol., September 1, 1999; 163(5): 2916 - 2921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Krco, S. Watanabe, J. Harders, M. M. Griffths, H. Luthra, and C. S. David Identification of T Cell Determinants on Human Type II Collagen Recognized by HLA-DQ8 and HLA-DQ6 Transgenic Mice J. Immunol., August 1, 1999; 163(3): 1661 - 1665. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
