Epitope specificity and T cell receptor usage in type II collagen induced autoimmune ear disease.
An immune response directed against type II collagen (CII) has been reported in several autoimmune diseases including the animal models of collagen-induced arthritis (CIA) and collagen-induced autoimmune ear disease (CIAED). In this communication, we have found that T cells from type II collagen-immunized DBA/1-lac could transfer auricular chondritis to naive mice. The T cells from type II collagen-immunized H-2r and H-2q mice recognize different epitopes from the CB11 peptide of CII. The CII-specific T cells from H-2q background mice recognize peptide residues p121-147 (P1) but do not respond to residues p211-247 (P2). The T cells of H-2r mice immunized with CII respond better to P2 rather than P1. By altering certain amino acids within these epitopes, the response of CII-specific TCR to antigen has been increased or abolished. Our results suggest that the lysine residues at positions 129, 141, and 147 in P1, the arginine residue at position 227, and glutamic acid at position 230 in P2 might play an important role in the trimolecular interaction. Ten clonally distinct T cell hybridomas specific for CII have been established from H-2r B10.RIII mice and the beta chains of their TCR have been analyzed. Three subfamilies, V beta 1, V beta 6, and V beta 8, were utilized with dominant expression of V beta 8 (60%). This is quite similar to the pattern found in type II collagen-induced arthritis in H-2q mice. This preferential use of V beta 8 in CIAED implies that an immunotherapy may make it possible to control this autoimmune disease, even in a MHC-diverse situation.
Yoo
T J
TJ
Department of Medicine, University of Tennessee, Memphis 38163.
Lee
M K
MK
Min
Y S
YS
Chiang
H J
HJ
Wang
K
K
Fujiyoshi
T
T
Watanabe
T
T
Krug
M S
MS
Seyer
J
J
Cheng
K C
KC
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D002357:Cartilage Diseases / Q000276:immunology / Q000473:pathology; D003094:Collagen / Q000276:immunology*; D004427:Ear Diseases / Q000276:immunology* / Q000473:pathology; D000939:Epitopes / Q000276:immunology*; D006825:Hybridomas; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013601:T-Lymphocytes / Q000502:physiology / Q000637:transplantation
D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003094:Collagen