αβ and γδ T cell receptors: Similar but different

Abstract

There are 2 populations of T lymphocytes, αβ T and γδ T cells, that can be distinguished by the expression of either an αβ TCR or a γδ TCR, respectively. Pairing of the Ag binding heterodimer, which consists of TCR‐α/TCR‐β (TCRαβ) or TCR‐γ/TCR‐δ (TCRγδ), with proteins of the CD3 complex forms the complete αβ or γδ TCR. Despite some similarities in the structure of TCRαβ and TCRγδ and the shared subunits of the CD3 complex, the 2 receptors differ in important aspects. These include the assembly geometry of the complex, the glycosylation pattern, the plasma membrane organization, as well as the accessibility of signaling motifs in the CD3 intracellular tails. These differences are reflected in the different demands and outcomes of ligand‐induced signaling. It was shown that exposure of the proline‐rich sequence (PRS) in CD3ε occurs with all activating αβ TCR ligands and is required to induce αβ TCR signaling. In sharp contrast, CD3ε PRS exposure was not induced by binding of those ligands to the γδ TCR that have been studied. Further, signaling by the γδ TCR occurs independently of CD3ε PRS exposure. Interestingly, it can be enhanced by anti‐CD3ε Ab‐induced enforcement of CD3ε PRS exposure. This review contrasts these two similar, but different immune receptors.

Anti-TRBC1 Antibody-Based Flow Cytometric Detection of T-Cell Clonality: Standardization of Sample Preparation and Diagnostic Implementation

“…Since both CD3 and anti-TRBC1 antibodies recognize physically close epitopes of the CD3/TCRαβ complex [36,37], we first tested the potential steric interaction between both groups of antibody reagents for optimization of the TRBC1 staining. Our results showed…”

“…Since both CD3 and anti-TRBC1 antibodies recognize physically close epitopes of the CD3/TCRαβ complex [36,37], we first tested the potential steric interaction between both groups of antibody reagents for optimization of the TRBC1 staining. Our results showed that addition of CD3 blocked the (low affinity/unspecific) binding of the anti-TRBC1 reagent to TRBC1 − (i.e., TRBC2 + ) Tαβ-cells [38], while similar percentages of TRBC1 + cells were observed in the absence vs. presence of the CD3 Mab.…”

Molecular design of the γδT cell receptor ectodomain encodes biologically fit ligand recognition in the absence of mechanosensing

“…27 and refs. therein), although some distinctions in CD3 heterodimers, FceRIγ and CD3ζ composition, may further tune signaling (53)(54)(55)(56). Replacement of CγCδ in WTDP10.7 γδTCR with CαCβ in the γδ-αβTCR construct confers αβTCR mechanosensing properties to the chimeric receptor whose VγVδ module (i.e., ligand interaction surface) remains the same.…”

“…Its receptors comprise ligand-binding subunit variants differing in their capacity to amplify bioforces and thus to modulate triggering of cellular activation using a comparable set of signaling (CD3) subunits. Other distinctions between TCRαβ and TCRγδ, including their connecting peptides and transmembrane segments (56), in addition to their ectodomains, might further nuance signaling differences.…”

Clonal Expansion of Bone Marrow CD8+ T Cells in Acute Myeloid Leukemia Patients at New Diagnosis and Post Chemotherapy

“…Notwithstanding the potential as a therapeutic target, CD8 + TCR repertoire dynamics and the modulation mechanisms of chemotherapy are still poorly understood. αβ T cells are the predominant subset, making up approximately 90-95% of all peripheral T cells in healthy adults [16]. Therefore, it is crucial to assess the characteristics of the CD8 + TCR repertoire and investigate the clinical signi cance in AML patients.…”