T Cell Activation Machinery: Form and Function in Natural and Engineered Immune Receptors

Chandler, Nicholas J; Call, Melissa; Call, Matthew E.

doi:10.3390/ijms21197424

Cited by 9 publications

(5 citation statements)

References 186 publications

(269 reference statements)

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“…For example, in CD28, the dimerization potential of the YxxxxT motif was reported to be comparable to that of glycophorin A’s GxxxG motif ( 34 , 54 , 55 ), the most common benchmark in TM helix dimerization. This has immediate clinical implications, because CD28 TM domains are used in chimeric antigen receptors (CARs) for cancer immunotherapy ( 56 , 57 ), where the YxxxxT motif drives unintended interactions between CARs and endogenous CD28 in patient T cells ( 35 , 58 ) and may thereby contribute to enhanced function ( 59 ) and/or toxicity ( 57 ).…”

Section: Discussionmentioning

confidence: 99%

T cell and B cell antigen receptors share a conserved core transmembrane structure

Ramesh

Park

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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The B cell and T cell antigen receptors (BCR and TCR) share a common architecture in which variable dimeric antigen-binding modules assemble with invariant dimeric signaling modules to form functional receptor complexes. In the TCR, a highly conserved T cell receptor αβ (TCRαβ) transmembrane (TM) interface forms a rigid structure around which its three dimeric signaling modules assemble through well-characterized polar interactions. Noting that the key features stabilizing this TCRαβ TM interface also appear with high evolutionary conservation in the TM sequences of the membrane immunoglobulin (mIg) heavy chains that form the BCR’s homodimeric antigen-binding module, we asked whether the BCR contained an analogous TM structure. Using an unbiased biochemical and computational modeling approach, we found that the mouse IgM BCR forms a core TM structure that is remarkably similar to that of the TCR. This structure is reinforced by a network of interhelical hydrogen bonds, and our model is nearly identical to the arrangement observed in the just-released cryo-electron microscopy (cryo-EM) structures of intact human BCRs. Our biochemical analysis shows that the integrity of this TM structure is vital for stable assembly with the BCR signaling module CD79AB in the B cell endoplasmic reticulum, and molecular dynamics simulations indicate that BCRs of all five isotypes can form comparable structures. These results demonstrate that, despite their many differences in composition, complexity, and ligand type, TCRs and BCRs rely on a common core TM structure that has been shaped by evolution for optimal receptor assembly and stability in the cell membrane.

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Section: Discussionmentioning

confidence: 99%

T cell and B cell antigen receptors share a conserved core transmembrane structure

Ramesh

Park

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…T cells amplified and activated in vitro, including cytokine-induced killer cells (CIK), TIL, and tumor antigen-specific CTL, can also be adopted into the tumor-bearing host. The most important achievement in this regard has been modified T cells based on chimeric antigen receptor (CAR) (CAR-T) [ 130 ]. In CAR T cell therapy, genetically engineered autologous T cells expressing CAR are used in patients.…”

Section: Immunotherapy Of Hncs Associated With T Cellsmentioning

confidence: 99%

T cell effects and mechanisms in immunotherapy of head and neck tumors

et al. 2023

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Head and neck tumors (HNCs) are a common tumor in otorhinolaryngology head and neck surgery, accounting for 5% of all malignant tumors in the body and are the sixth most common malignant tumor worldwide. In the body, immune cells can recognize, kill, and remove HNCs. T cell-mediated antitumor immune activity is the most important antitumor response in the body. T cells have different effects on tumor cells, among which cytotoxic T cells and helper T cells play a major killing and regulating role. T cells recognize tumor cells, activate themselves, differentiate into effector cells, and activate other mechanisms to induce antitumor effects. In this review, the immune effects and antitumor mechanisms mediated by T cells are systematically described from the perspective of immunology, and the application of new immunotherapy methods related to T cells are discussed, with the objective of providing a theoretical basis for exploring and forming new antitumor treatment strategies.

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“…However, a tight regulation of the immune response is essential to preserve the integrity of the organisms. Thus, T-cells suffering immunosenescent modifications 14 , chemotactic expansion, or exhaustion in response to physiological aging 15 , constant TCR triggering, costimulatory/inhibitory factors 16 can actually be responsible of immune dysregulation and contribute to different pathologies including a wide-variety of neoplasms 17 .…”

Section: Highlightsmentioning

confidence: 99%

Recent advances in T-cell lymphoid neoplasms

Bigas

Rodríguez‐Sevilla

Espinosa

et al. 2022

Experimental Hematology

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T Cell Activation Machinery: Form and Function in Natural and Engineered Immune Receptors

Cited by 9 publications

References 186 publications

T cell and B cell antigen receptors share a conserved core transmembrane structure

T cell and B cell antigen receptors share a conserved core transmembrane structure

T cell effects and mechanisms in immunotherapy of head and neck tumors

Recent advances in T-cell lymphoid neoplasms

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