It has been of much interest whether there is functional redundancy between the constitutively signaling pre-T␣/TCR␤ (pre-TCR) and ligated TCR␣␤ complexes, which independently operate the two distinct checkpoints during thymocyte development, i.e., the pre-TCR involved in ␤-selection at the CD4 ؊ CD8 ؊ double-negative stage and the TCR␣␤ being crucial for positive/negative selection at the CD4 ...

During alpha beta thymocyte development, the clonotypic alpha beta-T cell receptor (TCR) is preceded by sequentially expressed immature versions of the TCR-CD3 complex: the pre-TCR, containing a clonotypic TCR-beta chain and invariant pre-Talpha, is expressed on pre-T cells before rearrangement of the TCR-alpha locus. Moreover, clonotype-independent CD3 complexes (CIC) appear on pro-T cells bef...

Adoptive transfer of T cells that are gene engineered to express a defined TCR represents a feasible and promising therapy for patients with tumors. However, TCR gene therapy is hindered by the transient presence and effectiveness of transferred T cells, which are anticipated to be improved by adequate T cell costimulation. In this article, we report the identification and characterization of a...

T cell receptor (TCR)-gene-modified T cells for adoptive cell transfer can mediate objective clinical responses in melanoma and other malignancies. When introducing a second TCR, mispairing between the endogenous and introduced α and β TCR chains limits expression of the introduced TCR, which can result in impaired efficacy or off-target reactivity and autoimmunity. One approach to promote prop...

TCR gene modified T cells for adoptive therapy simultaneously express the Tg TCR and the endogenous TCR, which might lead to mispaired TCRs with harmful unknown specificity and to a reduced function of TCR-Tg T cells. We generated dual TCR T cells in two settings in which either TCR was constitutively expressed by a retroviral promoter while the second TCR expression was regulable by a Tet-on s...

We have examined the expression of the recombination activating gene RAG-1 by in situ hybridization to thymi from mice bearing transgenes for the T-cell receptor (TCR) alpha chain, TCR beta chain, or both TCR alpha and beta chains. RAG-1 transcription was found in the thymic cortex of transgenic mice carrying a single TCR alpha- or TCR beta-chain transgene, comparable to normal mice. However, R...

Antigen-specific suppressor T-cell hybridomas release soluble suppressor factors (TsF) in the supernatant that modulate both in vivo delayed-type hypersensitivity and in vitro plaque-forming cell responses in an antigen-specific manner. To study the relationship between the T-cell receptor (TcR) and TsF, we developed a series of TcR alpha- or TcR beta- expression variants from suppressor T-cell...

T lymphocytes (T cells) are the major mediators of adaptive immune response. They detect pathogens primarily via interaction their cell receptor (TCR) with cognate pathogen-derived peptide displayed in context MHC on infected cell. A critical step activation is formation immunological synapse, a specialized cell–cell conjugate interface between and cell, where massive TCR-induced actin remodeli...

T cells engineered to express a tumor-specific αβ T cell receptor (TCR) mediate anti-tumor immunity. However, mispairing of the therapeutic αβ chains with endogenous αβ chains reduces therapeutic TCR surface expression and generates self-reactive TCRs. We report a general strategy to prevent TCR mispairing: swapping constant domains between the α and β chains of a therapeutic TCR. When paired, ...