Definition of MHC and T cell receptor contacts in the HLA-DR4restricted immunodominant epitope in type II collagen and characterization of collagen-induced arthritis in HLA-DR4 and human CD4 transgenic mice.
Rheumatoid arthritis (RA) is an autoimmune disease associated with the HLA-DR4 and DR1 alleles. The target autoantigen(s) in RA is unknown, but type II collagen (CII) is a candidate, and the DR4- and DR1-restricted immunodominant T cell epitope in this protein corresponds to amino acids 261-273 (CII 261-273). We have defined MHC and T cell receptor contacts in CII 261-273 and provide strong evidence that this peptide corresponds to the peptide binding specificity previously found for RA-associated DR molecules. Moreover, we demonstrate that HLA-DR4 and human CD4 transgenic mice homozygous for the I-Abbeta0 mutation are highly susceptible to collagen-induced arthritis and describe the clinical course and histopathological changes in the affected joints.
Andersson
E C
EC
Departments of Clinical Immunology, Rigshospitalet, 2200 N Copenhagen, Denmark.
Hansen
B E
BE
Jacobsen
H
H
Madsen
L S
LS
Andersen
C B
CB
Engberg
J
J
Rothbard
J B
JB
McDevitt
G S
GS
Malmström
V
V
Holmdahl
R
R
Svejgaard
A
A
Fugger
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003094:Collagen / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains; D016056:Immunodominant Epitopes; D011948:Receptors, Antigen, T-Cell; D003094:Collagen