TCR gene usage in experimental autoimmune myasthenia gravis pathogenesis

Usage of multiple TCRBV genes in the H-2b strains

B. Wu, M. Shenoy, E. Goluszko, R. Kaul, P. Christadoss

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Experimental autoimmune myasthenia gravis (EAMG) is an Ab-mediated autoimmune disease. The pathogenic auto-antibody production depends on the activation of CD4+ cells after their TCR interact with dominant T cell epitopes within acetylcholine receptor (AChR) in the context of the MHC class II molecule. In vitro analysis suggested that the TCRBV6 was the predominant TCR that recognized AChR and one of the dominant epitopes, α146-162, in C57BL6 (B6, H-2b) mice. However, in vivo depletion of TCRBV6 cells in H-2b mice by anti-TCRBV6 mAb neither suppressed the in vitro immune response to AChR nor prevented development of EAMG. Moreover, B10.TCR(c) (H-2b) strain with a genomic deletion of TCRBV genes including TCRBV6, and B10.Vβ8.2 transgenic mice with a restricted TCRBV8S2 T cell repertoire, responded to AChR, α146-162, and developed EAMG after immunizations with AChR/CFA. These data suggest that more than one TCRBV-bearing cell having the affinity for AChR-dominant peptides is involved in pathogenesis. Therefore, depletion of a single TCRBV (e.g., TCRBV6) with mAb may not be sufficient to completely suppress the response to AChR and development of EAMG. However, if a similar amino acid sequence in the TCR-VDJ (e.g., CDR3) region among different TCRBV gene(s) could be involved in recognizing the dominant AChR epitope(s), then motif-specific mAb reactive to the common motif within the VDJ region of different TCR could be used to eliminate the T cell clones involved in EAMG.

Original languageEnglish (US)
Pages (from-to)3603-3610
Number of pages8
JournalJournal of Immunology
Volume154
Issue number7
StatePublished - 1995

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Autoimmune Experimental Myasthenia Gravis
Cholinergic Receptors
Genes
Epitopes
T-Lymphocytes
T-Lymphocyte Epitopes
Gene Deletion
Transgenic Mice
Autoimmune Diseases
Antibody Formation
Amino Acid Sequence
Immunization
Clone Cells
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

TCR gene usage in experimental autoimmune myasthenia gravis pathogenesis : Usage of multiple TCRBV genes in the H-2b strains. / Wu, B.; Shenoy, M.; Goluszko, E.; Kaul, R.; Christadoss, P.

In: Journal of Immunology, Vol. 154, No. 7, 1995, p. 3603-3610.

Research output: Contribution to journalArticle

Wu, B, Shenoy, M, Goluszko, E, Kaul, R & Christadoss, P 1995, 'TCR gene usage in experimental autoimmune myasthenia gravis pathogenesis: Usage of multiple TCRBV genes in the H-2b strains', Journal of Immunology, vol. 154, no. 7, pp. 3603-3610.
Wu, B. ; Shenoy, M. ; Goluszko, E. ; Kaul, R. ; Christadoss, P. / TCR gene usage in experimental autoimmune myasthenia gravis pathogenesis : Usage of multiple TCRBV genes in the H-2b strains. In: Journal of Immunology. 1995 ; Vol. 154, No. 7. pp. 3603-3610.
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