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

Xiaowen He, Edward F. Rosloniec, Linda Myers, William Lewis McColgan, Marina Gumanovskaya, Andrew Kang, John Stuart

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 Vβ-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 Vβ- and V α-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. 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 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 V α genes, although this was less marked than that of V β. In contrast, the hybridomas expressed a diverse third complementarity-determining region. Deletion of both Vβ 14-bearing and Vβ8-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.

Original languageEnglish (US)
Pages (from-to)1996-2004
Number of pages9
JournalArthritis and rheumatism
Volume50
Issue number6
DOIs
StatePublished - Jun 1 2004

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Collagen Type II
HLA-DR Antigens
T-Cell Antigen Receptor
Transgenic Mice
Hybridomas
T-Lymphocytes
Experimental Arthritis
Complementarity Determining Regions
Peptide T
Immunodominant Epitopes
Peptides
T-Lymphocyte Subsets
Genes
Arthritis
Complementary DNA
RNA
Polymerase Chain Reaction
Antibodies
Incidence

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

T cell receptors recognizing type II collagen in HLA-DR-transgenic mice characterized by highly restricted Vβ usage. / He, Xiaowen; Rosloniec, Edward F.; Myers, Linda; McColgan, William Lewis; Gumanovskaya, Marina; Kang, Andrew; Stuart, John.

In: Arthritis and rheumatism, Vol. 50, No. 6, 01.06.2004, p. 1996-2004.

Research output: Contribution to journalArticle

He, Xiaowen ; Rosloniec, Edward F. ; Myers, Linda ; McColgan, William Lewis ; Gumanovskaya, Marina ; Kang, Andrew ; Stuart, John. / T cell receptors recognizing type II collagen in HLA-DR-transgenic mice characterized by highly restricted Vβ usage. In: Arthritis and rheumatism. 2004 ; Vol. 50, No. 6. pp. 1996-2004.
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