T cell receptor (TCR) beta genes are rearranged prior to TCR alpha genes. A productively rearranged TCR beta gene suppresses further V beta gene rearrangement. Here we show that in beta TCR transgenic mice the TCR beta-chain can be expressed on the surface of immature CD4-8- thymocytes, but not on mature T cells, in the absence of any other known TCR chain and proteins of the CD3 complex. Analysis by NEPHGE and SDS-PAGE showed that at least some beta TCR exists on the surface as a large disulfide-linked complex with unknown acidic molecules. The introduction of the beta TCR gene into scid mice resulted in the expression of the beta TCR on the cell surface of thymocytes and induced the expression of CD4 and CD8 co-receptors as well as transcription of the alpha TCR locus.
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http://dx.doi.org/10.1002/j.1460-2075.1991.tb07924.x | DOI Listing |
Immunol Rev
January 2025
Department of Chemistry and Biochemistry and the Harper Cancer Research Institute, University of Notre Dame, Notre Dame, Indiana, USA.
αβ T cell receptor (TCR) recognition of peptide-MHC complexes lies at the core of adaptive immunity, balancing specificity and cross-reactivity to facilitate effective antigen discrimination. Early structural studies established basic frameworks helpful for understanding and contextualizing TCR recognition and features such as peptide specificity and MHC restriction. However, the growing TCR structural database and studies launched from structural work continue to reveal exceptions to common assumptions and simplifications derived from earlier work.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Cytopathology, Institute of Oncology, Zaloška Cesta 2, 1000 Ljubljana, Slovenia.
Flow cytometric (FC) immunophenotyping and T-cell receptor (TCR) gene rearrangement studies are essential ancillary methods for the characterisation of T-cell lymphomas. Traditional manual gating and polymerase chain reaction (PCR)-based analyses can be labour-intensive, operator-dependent, and have limitations in terms of sensitivity and specificity. The objective of our study was to investigate the efficacy of the Phenograph and t-SNE algorithms together with an antibody specific for the TCR β-chain constant region 1 (TRBC1) to identify monoclonal T-cell populations.
View Article and Find Full Text PDFPLoS One
January 2025
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
T cell immunotherapy success is dependent on effective levels of antigen receptor expressed at the surface of engineered cells. Efforts to optimize surface expression in T cell receptor (TCR)-based therapeutic approaches include optimization of cellular engineering methods and coding sequences, and reducing the likelihood of exogenous TCR α and β chains mispairing with the endogenous TCR chains. Approaches to promote correct human TCR chain pairing include constant region mutations to create an additional disulfide bond between the two chains, full murinization of the constant region of the TCR α and β sequences, and a minimal set of murine mutations to the TCR α and β constant regions.
View Article and Find Full Text PDFCell Death Differ
January 2025
Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
The assembly of Tcrb and Tcra genes require double negative (DN) thymocytes to undergo multiple rounds of programmed DNA double-strand breaks (DSBs), followed by their efficient repair. However, mechanisms governing cell cycle checkpoints and specific survival pathways during the repair process remain unclear. Here, we report high-resolution scRNA-seq analyses of individually sorted mouse DN3 and DN4 thymocytes, which reveals a G2M cell cycle checkpoint, in addition to the known G1 checkpoint, during Tcrb and Tcra recombination.
View Article and Find Full Text PDFClin Exp Med
January 2025
Guangzhou Huayin Health Medical Group Co., Ltd, Guangzhou, 510515, China.
Coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) has been observed in some chronic hepatitis B (CHB) patients (DP patients), but the clinical outcomes and comprehensive characterization of immune micro-environmental changes for this specific population remain inconclusive. In this study, we retrospectively analyze the prognosis of 305 patients in Foshan City, Guangdong Province, China, and also investigated the molecular immunology changes in HBsAg and anti-HBs double positive CHB patients (DP group), CHB patients who had recovered from IFN-ɑ treatment (RP group), and healthy controls (HC group) using T cell receptor (TCR) and B cell receptor (BCR) immune repertoire sequencing. Our findings revealed that 22.
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