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

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.

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

Journal of Experimental Medicine ◽

10.1084/jem.187.2.253 ◽

1998 ◽

Vol 187 (2) ◽

pp. 253-258 ◽

Cited By ~ 14

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.

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

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1999.1128 ◽

1999 ◽

Vol 263 (1) ◽

pp. 172-180 ◽

Cited By ~ 11

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

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

Molecular Cancer ◽

10.1186/s12943-020-01282-7 ◽

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.

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Diversity of T cell receptor α and β chain genes expressed by human T cells specific for similar myelin basic protein peptide/major histocompatibility complexes

European Journal of Immunology ◽

10.1002/eji.1830220319 ◽

1992 ◽

Vol 22 (3) ◽

pp. 753-758 ◽

Cited By ~ 56

Author(s):

Gerhard Giegerich ◽

Martin Pette ◽

Edgar Meinl ◽

Jörg T. Epplen ◽

Hartmut Wekerle ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Myelin Basic Protein ◽

T Cell Receptor ◽

Basic Protein ◽

Cell Receptor ◽

Major Histocompatibility ◽

Human T Cells ◽

Major Histocompatibility Complexes ◽

Β Chain

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

Immunology ◽

10.1111/imm.12067 ◽

2013 ◽

Vol 139 (3) ◽

pp. 309-317 ◽

Cited By ~ 8

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

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Influence of T cell receptor V alpha expression on Mlsa superantigen-specific T cell responses.

Journal of Experimental Medicine ◽

10.1084/jem.175.5.1405 ◽

1992 ◽

Vol 175 (5) ◽

pp. 1405-1408 ◽

Cited By ~ 51

Author(s):

M S Vacchio ◽

O Kanagawa ◽

K Tomonari ◽

R J Hodes

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Receptor ◽

Variable Region ◽

Cell Receptor ◽

Variable Regions ◽

Peripheral T Cells ◽

Multiple Variable ◽

Alpha Beta

Recognition of conventional foreign antigen by T cells is determined by the expression of multiple variable regions of both alpha and beta chains of the T cell receptor (TCR) alpha/beta heterodimer. In contrast, there exists a class of antigens that appears to interact with the TCR alpha/beta heterodimer through the variable region on the beta chain (V beta), independent of other TCR components, a property that has led to their designation as superantigens. The goal of the present study was to analyze V alpha use in V beta 6+ T cells responsive to the superantigen, Mlaa. Results indicate that while deletion of T cells expressing V beta 6 in Mlsa-expressing mice is essentially complete and therefore appears to occur regardless of V alpha usage, in vitro Mlsa stimulation of T cells from Mlsa-negative mice results in significant skewing of V alpha use among responding V beta 6+ T cells. This indicates that V alpha expression influences recognition of the superantigen, Mlsa by mature peripheral T cells.

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