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

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.

1999 ◽  
Vol 263 (1) ◽  
pp. 172-180 ◽  
Author(s):  
Toru Mima ◽  
Shiro Ohshima ◽  
Mitsuko Sasai ◽  
Katsuhiro Nishioka ◽  
Masatoshi Shimizu ◽  
...  

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3737-3744 ◽  
Author(s):  
Johan Grunewald ◽  
Eva Halapi ◽  
Jan Wahlström ◽  
Ricardo Giscombe ◽  
Soniya Nityanand ◽  
...  

T lymphocytes are implicated in the pathogenesis of systemic vasculitis such as Wegener’s granulomatosis (WG) and polyarteritis nodosa (PAN). In the present study, we have characterized in detail the T-cell receptor (TCR) of peripheral blood T cells from eight vasculitis patients of known HLA class II genotypes. We used flow cytometry to outline the exact TCR V gene expression, complementarity determining region 3 (CDR3) fragment analysis to estimate the degree of clonality and cDNA sequencing to define the exact TCR  or β chain sequences. The TCR CDR3 region interacts with antigenic peptides presented by HLA molecules, and it is normally immensely diverse. It was therefore of particular interest to identify a common dominating TCR BV8-F/L-G-G-A/Q-G-J2S3 β chain sequence in the CD4+T cells of four unrelated vasculitis patients. Furthermore, this BV8-associated CDR3 motif was linked to the HLA-DRB1*0401 allele, as well as to active disease and/or an established BV8+ CD4+ T-cell expansion. In contrast, age- and HLA-matched patients with rheumatoid arthritis did not harbor the described BV8 motif. These results strongly suggest that BV8+ CD4+ T cells with the described CDR3 motif recognize a specific antigen presented by DR4 molecules, indicating the existence of a common vasculitis-associated antigen.


Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3737-3744 ◽  
Author(s):  
Johan Grunewald ◽  
Eva Halapi ◽  
Jan Wahlström ◽  
Ricardo Giscombe ◽  
Soniya Nityanand ◽  
...  

Abstract T lymphocytes are implicated in the pathogenesis of systemic vasculitis such as Wegener’s granulomatosis (WG) and polyarteritis nodosa (PAN). In the present study, we have characterized in detail the T-cell receptor (TCR) of peripheral blood T cells from eight vasculitis patients of known HLA class II genotypes. We used flow cytometry to outline the exact TCR V gene expression, complementarity determining region 3 (CDR3) fragment analysis to estimate the degree of clonality and cDNA sequencing to define the exact TCR  or β chain sequences. The TCR CDR3 region interacts with antigenic peptides presented by HLA molecules, and it is normally immensely diverse. It was therefore of particular interest to identify a common dominating TCR BV8-F/L-G-G-A/Q-G-J2S3 β chain sequence in the CD4+T cells of four unrelated vasculitis patients. Furthermore, this BV8-associated CDR3 motif was linked to the HLA-DRB1*0401 allele, as well as to active disease and/or an established BV8+ CD4+ T-cell expansion. In contrast, age- and HLA-matched patients with rheumatoid arthritis did not harbor the described BV8 motif. These results strongly suggest that BV8+ CD4+ T cells with the described CDR3 motif recognize a specific antigen presented by DR4 molecules, indicating the existence of a common vasculitis-associated antigen.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jing Ye ◽  
Dengming Lai ◽  
Dan Cao ◽  
Linhua Tan ◽  
Lei Hu ◽  
...  

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.


2001 ◽  
Vol 75 (2) ◽  
pp. 1065-1071 ◽  
Author(s):  
Mineki Saito ◽  
Graham P. Taylor ◽  
Akiko Saito ◽  
Yoshitaka Furukawa ◽  
Koichiro Usuku ◽  
...  

ABSTRACT Using HLA-peptide tetrameric complexes, we isolated human T-cell lymphotrophic virus type 1 Tax peptide-specific CD8+ T cells ex vivo. Antigen-specific amino acid motifs were identified in the T-cell receptor Vβ CDR3 region of clonally expanded CD8+ T cells. This result directly confirms the importance of the CDR3 region in determining the antigen specificity in vivo.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Chaoting Zhang ◽  
Heyilimu Palashati ◽  
Zhuona Rong ◽  
Ningjing Lin ◽  
Luyan Shen ◽  
...  

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.


1995 ◽  
Vol 187 (1) ◽  
pp. 139-150 ◽  
Author(s):  
Debang Liu ◽  
James P. Callahan ◽  
Peter C. Dau

2014 ◽  
Vol 67 (2) ◽  
pp. 95-109 ◽  
Author(s):  
Carolyn T. A. Herzig ◽  
Vanessa L. Mailloux ◽  
Cynthia L. Baldwin

Immunology ◽  
2013 ◽  
Vol 139 (3) ◽  
pp. 309-317 ◽  
Author(s):  
Yusuke Okuno ◽  
Ayako Murakoshi ◽  
Masashi Negita ◽  
Kazuyuki Akane ◽  
Seiji Kojima ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document