Dominant and Shared T Cell Receptor β Chain Variable Regions of T Cells Inducing Synovial Hyperplasia in Rheumatoid Arthritis

1999 ◽  
Vol 263 (1) ◽  
pp. 172-180 ◽  
Author(s):  
Toru Mima ◽  
Shiro Ohshima ◽  
Mitsuko Sasai ◽  
Katsuhiro Nishioka ◽  
Masatoshi Shimizu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Variable Regions ◽  
Synovial Hyperplasia ◽  
Β Chain

scholarly journals Highly Biased CDR3 Usage in Restricted Sets of β Chain Variable Regions During Viral Superantigen 9 Response

1998 ◽  
Vol 187 (2) ◽  
pp. 253-258 ◽  
Author(s):  
Cristina Ciurli ◽  
David N. Posnett ◽  
Rafick-Pierre Sékaly ◽  
François Denis
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Hypervariable Region ◽  
Cell Receptor ◽  
Variable Regions ◽  
Cdr3 Region ◽  
Tumor Virus ◽  
The One ◽  
Β Chain

Superantigens encoded by the mouse mammary tumor virus can stimulate a large proportion of T cells through interaction with germline-encoded regions of the T cell receptor β chain like the hypervariable region 4 (HV4) loop. However, several lines of evidence suggest that somatically generated determinants in the CDR3 region might influence superantigen responses. We stimulated T cells from donors differing at the BV6S7 allele with vSAG9 to assess the nature and structure of the T cell receptor in amplified T cells and to evaluate the contribution of non-HV4 elements in vSAG recognition. This report demonstrates that vSAG9 stimulation caused the expansion of TCR BV6-expressing T cells, although to varying degrees depending on the BV6 subfamily. The BV6S7 subfamily was preferentially expanded in all donors, but in donors homozygous for the BV6S7*2 allele, a significant number of BV6S5 T cells were amplified and showed a highly biased β chain junctional region (BJ) and CDR3 usage. As CDR3 regions are involved in major histocompatibility complex (MHC)–peptide interaction, such a selection is highly suggestive of an intimate MHC–TCR interaction and would imply that the topology of the MHC-vSAG-TCR complex is similar to the one occurring during conventional antigen recognition.

scholarly journals Altered T-Cell Receptor β-Chain and Lactate Dehydrogenase Are Associated With the Immune Pathogenesis of Biliary Atresia

2021 ◽  
Vol 8 ◽  
Author(s):  
Jing Ye ◽  
Dengming Lai ◽  
Dan Cao ◽  
Linhua Tan ◽  
Lei Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Lactate Dehydrogenase ◽  
T Cell ◽  
Biliary Atresia ◽  
T Cell Receptor ◽  
High Throughput Sequencing ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Variable Regions ◽  
Β Chain

Background: Biliary atresia (BA) is considered to be an autoimmune-mediating inflammatory injury. The pathogenesis of BA has been proposed with the clonal transformation of T cells expressing analogous T-cell receptor β-chain variable regions (TRBVs).Methods: The TRBV profile of the peripheral blood mononuclear cells (PBMCs) in infants with BA and control infants (healthy donors, HDs), respectively, were characterized by using high-throughput sequencing (HTS). The diversity of T cells was analyzed based on the frequency of complementarity-determining region 3 (CDR3) or V(CDR3)J. Moreover, the correlation between absolute lymphocyte count (ALC) and lactate dehydrogenase (LDH) or diversity (clonality) indices, respectively, were analyzed for subjects with BA and HD.Results: The diversity indices of CDR3, V(CDR3)J in BA are lower than those in subjects with HD, in addition, there are significantly different levels of neutrophile, neutrophile/lymphocyte ratio (NLR), and LDH between groups of BA and HD. The correlation between ALC and diversity index is significant in subjects with HD but is not for subjects with BA. Conversely, the relationship between ALC and LDH is significant in subjects with BA but is not for subjects with HD. Moreover, 12 CDR3 motifs are deficient or lower expression in BA compared with that in the HD group.Conclusion: Our results demonstrate that the profile of TRBV repertoire is significantly different between subjects with BA and HD, and suggest that the immune imbalance and elevated LDH level are associated with the pathogenesis of BA. Moreover, the values of neutrophile, NLR, and LDH could be used for the differential diagnosis of BA.

T-cell receptor variable region of the β-chain gene use in peripheral blood and multiple synovial membranes during rheumatoid arthritis

1995 ◽  
Vol 42 (4) ◽  
pp. 331-339 ◽  
Author(s):  
Antoine Alam ◽  
Jacqueline Lulé ◽  
Héléne Coppin ◽  
Nathalie Lambert ◽  
Bernard Maziéres ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
Variable Region ◽  
Cell Receptor ◽  
Chain Gene ◽  
Synovial Membranes ◽  
Β Chain

scholarly journals Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Chaoting Zhang ◽  
Heyilimu Palashati ◽  
Zhuona Rong ◽  
Ningjing Lin ◽  
Luyan Shen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Therapeutic Efficacy ◽  
Terminal Differentiation ◽  
Cell Receptor ◽  
Constant Region ◽  
Car T ◽  
T Cell Malignancies ◽  
Β Chain

AbstractTargeting T cell receptor β-chain constant region 1 (TRBC1) CAR-T could specifically kill TRBC1+ T-cell malignancies. However, over-expressed CARs on anti-TRBC1 CAR transduced TRBC1+ T cells (CAR-C1) bound to autologous TRBC1, masking TRBC1 from identification by other anti-TRBC1 CAR-T, and moreover only the remaining unoccupied CARs recognized TRBC1+ cells, considerably reducing therapeutic potency of CAR-C1. In addition, co-culture of anti-TRBC1 CAR-T and TRBC1+ cells could promote exhaustion and terminal differentiation of CAR-T. These findings provide a rationale for pre-depleting TRBC1+ T cells before anti-TRBC1 CAR-T manufacturing.

scholarly journals CD8+ CD122+regulatory T cells contain clonally expanded cells with identical CDR3 sequences of the T-cell receptor β-chain

Immunology ◽  
2013 ◽  
Vol 139 (3) ◽  
pp. 309-317 ◽  
Author(s):  
Yusuke Okuno ◽  
Ayako Murakoshi ◽  
Masashi Negita ◽  
Kazuyuki Akane ◽  
Seiji Kojima ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Β Chain

scholarly journals TCR repertoire analysis reveals effector memory T cells differentiation into Th17 cells in rheumatoid arthritis

2019 ◽  
Author(s):  
Xu Jiang ◽  
Shi-yu Wang ◽  
Chen Zhou ◽  
Jing-hua Wu ◽  
Yu-hao Jiao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Th17 Cells ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Systemic Autoimmune Disease ◽  
Autoreactive T Cell

AbstractThe pathogenesis of rheumatoid arthritis (RA), a systemic autoimmune disease characterized by autoreactive T-cell accumulation and pro-inflammatory cytokine overproduction, is unclear. Systematically addressing T-cell receptor (TCR) repertoires of different CD4+ T-cell subsets could help understand RA pathogenesis. Here, peripheral CD4+ T cells from treatment-naïve RA patients and healthy controls were sorted into seven subsets including naïve, effector, central memory, effector memory (EMT), Th1, Th17, and regulatory T cells. T-cell receptor β chain repertoires were then analyzed by next-generation sequencing. We identified T-cell clonal expansion in EMT and Th17 cells, with highly similar TCR repertoires between them. Ex vivo experiments demonstrated the preferred differentiation from EMT to Th17 cells in RA. Moreover, TCR diversity in subsets including Th17 was negatively correlated with RA disease activity indices such as C-reactive protein and erythrocyte sedimentation rate. Thus, shared and abnormally expanded EMT and Th17 TCR repertoires might be pivotal for RA pathogenesis.

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