TY - JOUR
T1 - TCR gene usage in experimental autoimmune myasthenia gravis pathogenesis
T2 - Usage of multiple TCRBV genes in the H-2b strains
AU - Wu, Bo
AU - Shenoy, Mohan
AU - Goluszko, Elzbieta
AU - Kaul, Rashmi
AU - Christadoss, Premkumar
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
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M3 - Article
C2 - 7897239
AN - SCOPUS:0028935577
SN - 0022-1767
VL - 154
SP - 3603
EP - 3610
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -