T cell receptors recognizing type II collagen in HLA-DR-transgenic mice characterized by highly restricted V beta usage.
OBJECTIVE
To determine the T cell receptor (TCR) structure recognizing type II collagen (CII) in HLA-DR-transgenic mice, and to examine the role of T cells with certain V(beta)-chains in collagen-induced arthritis (CIA).


METHODS
T cell hybridomas were established from DR1- and DR4-transgenic mice and selected for their responses to CII and CII peptide containing the T cell determinants. RNA was extracted and reverse transcribed into complementary DNA, which was then amplified using appropriate V(beta)- and V(alpha)-subfamily-specific primers. The polymerase chain reaction products were purified and directly sequenced. To determine the role of T cells with certain V(beta)-chains in CIA, V(beta)-subfamily-specific antibodies were administered and the development and characteristics of arthritis were determined.


RESULTS
TCRs of 23 clonally distinct T cell hybridomas that were derived from DR1-transgenic mice and that were reactive to the CII peptide containing the immunodominant determinant were analyzed. These hybridomas predominantly used the TCR V(beta)14 and V(beta)8 gene segments (70% and 30%, respectively). The same restriction in V(beta) usage was also found in CII-reactive T cell hybridomas from DR4-transgenic mice. There was also restricted use of V(alpha) genes, although this was less marked than that of V(beta). In contrast, the hybridomas expressed a diverse third complementarity-determining region. Deletion of both V(beta)14-bearing and V(beta)8-bearing T cells significantly reduced the incidence and severity of CIA.


CONCLUSIONS
These data demonstrate that DR1 and DR4 not only bind and present the same CII immunodominant peptide, but also stimulate a highly restricted subset of T cells.
He
Xiaowen
X
Research Service, Memphis Veterans Affairs Medical Center, and University of Tennessee, 38104, USA. xhe@utmem.edu
Rosloniec
Edward F
EF
Myers
Linda K
LK
McColgan
William Lewis
WL
Gumanovskaya
Marina
M
Kang
Andrew H
AH
Stuart
John M
JM
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D024043:Collagen Type II / Q000276:immunology / Q000378:metabolism*; D022801:Complementarity Determining Regions / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D015798:HLA-DR1 Antigen / Q000235:genetics* / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000235:genetics* / Q000276:immunology; D006801:Humans; D006825:Hybridomas; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D024043:Collagen Type II; D022801:Complementarity Determining Regions; D015798:HLA-DR1 Antigen; D015804:HLA-DR4 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta