T cell receptors recognizing type II collagen in HLA–DR–transgenic mice characterized by highly restricted Vβ usage

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Abstract
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 Vβ-chains in collagen-induced arthritis (CIA). 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 Vβ- and Vα-subfamily–specific primers. The polymerase chain reaction products were purified and directly sequenced. To determine the role of T cells with certain Vβ-chains in CIA, Vβ-subfamily–specific antibodies were administered and the development and characteristics of arthritis were determined. 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 Vβ14 and Vβ8 gene segments (70% and 30%, respectively). The same restriction in Vβ usage was also found in CII-reactive T cell hybridomas from DR4-transgenic mice. There was also restricted use of Vα genes, although this was less marked than that of Vβ. In contrast, the hybridomas expressed a diverse third complementarity-determining region. Deletion of both Vβ14-bearing and Vβ8-bearing T cells significantly reduced the incidence and severity of CIA. 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.

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