scholarly journals Hybrid T cell receptor genes formed by interlocus recombination in normal and ataxia-telangiectasis lymphocytes.

1990 ◽  
Vol 172 (2) ◽  
pp. 409-418 ◽  
Author(s):  
S Lipkowitz ◽  
M H Stern ◽  
I R Kirsch

In this paper, using polymerase chain reaction (PCR), we demonstrated the occurrence of hybrid genes formed by interlocus recombination between T cell receptor gamma (TCR-gamma) variable (V) regions and TCR-beta joining (J) regions in the peripheral blood lymphocytes (PBL) from normal individuals and patients with ataxia-telangiectasia (AT). Sequence analysis of the PCR-derived hybrid genes confirmed that site-specific V gamma-J beta recombination had occurred and showed that 10 of 23 genomic hybrid genes maintained a correct open reading frame. By dilution analysis, the frequency of these hybrid genes was 8 +/- 1/10(5) cells in normal PBL and 587 +/- 195/10(5) cells in AT PBL. These frequencies and the approximately 70-fold difference between the normal and AT samples are consistent with previous cytogenetic data examining the occurrence of an inversion of chromosome 7 in normal and AT PBL. We also demonstrated expression of these hybrid genes by PCR analysis of first-strand cDNA prepared from both normal and AT PBL. Sequence analysis of the PCR-amplified transcripts showed that, in contrast to the genomic hybrid genes, 19 of 22 expressed genes maintained a correct open reading frame at the V-J junction and correctly spliced the hybrid V-J exon to a TCR-beta constant region, thus allowing translation into a potentially functional hybrid TCR protein. Another type of hybrid TCR transcript was found in a which a rearranged TCR-gamma V-J exon was correctly spliced to a TCR-beta constant region. This form of hybrid gene may be formed by trans-splicing. These hybrid TCR genes may serve to increase the repertoire of the immune response. In addition, studies of their mechanism of formation and its misregulation in AT may provide insight into the nature of the chromosomal instability syndrome associated with AT. The mechanism underlying hybrid gene formation may be analogous to the mechanism underlying rearrangements between putative growth-affecting genes and the antigen receptor loci, which are associated with AT lymphocyte clones and lymphoid malignancies.

1990 ◽  
Vol 31 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Naotaka Ishiguro ◽  
Astuko Tanaka ◽  
Morikazu Shinagawa

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.


1994 ◽  
Vol 40 (3) ◽  
pp. 323-336 ◽  
Author(s):  
S. CASPAR-BAUGUIL ◽  
J. ARNAUD ◽  
A. HUCHENQ ◽  
W. R. HEIN ◽  
C. GEISLER ◽  
...  

1988 ◽  
Vol 18 (4) ◽  
pp. 641-644 ◽  
Author(s):  
Henrik Griesser ◽  
Erik Champagne ◽  
Douglas Tkachuk ◽  
Yoshihiro Takihara ◽  
Marc Lalande ◽  
...  

1986 ◽  
Vol 16 (7) ◽  
pp. 851-854 ◽  
Author(s):  
Andre Traunecker ◽  
Beatrice Dolder ◽  
Klaus Karjalainen

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3433-3440 ◽  
Author(s):  
Wing-Shing Cheng ◽  
Valeria Giandomenico ◽  
Ira Pastan ◽  
Magnus Essand

Abstract TARP (T cell receptor γ-chain alternate reading frame protein) is uniquely expressed in males in prostate epithelial cells and prostate cancer cells. Here we demonstrate that TARP expression is regulated by testosterone at the transcriptional level through specific binding of androgen receptor to an androgen response element in the proximal TARP promoter. We further demonstrate that the promoter specifically initiates reporter gene expression in TARP-positive prostate cancer cell lines. To develop a regulatory sequence for prostate-specific gene expression, we constructed a chimeric sequence consisting of the TARP promoter and the prostate-specific antigen (PSA) enhancer. We found that in the prostatic adenocarcinoma cell line LNCaP, the transcriptional activity of the regulatory sequence consisting of a TARP promoter and PSA enhancer is 20 times higher than the activity of a regulatory sequence consisting of the PSA promoter and PSA enhancer. Thus, our studies define a regulatory sequence that may be used to restrict expression of therapeutic genes to prostate cancer cells and may therefore play a role in prostate cancer gene therapy.


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