T cell receptors recognizing type II collagen in HLA–DR–transgenic mice characterized by highly restricted Vβ usage
✍ Scribed by Xiaowen He; Edward F. Rosloniec; Linda K. Myers; William Lewis McColgan III; Marina Gumanovskaya; Andrew H. Kang; John M. Stuart
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 145 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
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  -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  -and V ␣ -subfamily-specific primers. The polymerase chain reaction products were purified and directly sequenced. To determine the role of T cells with certain V  -chains in CIA, V  -subfamilyspecific 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  14 and V  8 gene segments (70% and 30%, respectively). The same restriction in V  usage was also found in CIIreactive T cell hybridomas from DR4-transgenic mice. There was also restricted use of V ␣ genes, although this was less marked than that of V  . In contrast, the hybridomas expressed a diverse third complementaritydetermining region. Deletion of both V  14-bearing and V  8-bearing T cells significantly reduced the incidence and severity of CIA.
Conclusion. 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.