Other Receptors

γδ T cells are attractive targets for cellular immunotherapy. According to how extensive researches reported, γδ T cells receptors play important roles in γδ T cells activation, immune activities, modulation... Thus, it is necessary to explore more about γδ T cells receptors.

Introduction to γδ T Cells Receptors

T cell responses to a broad variety of pathogens as well as to cancer cells are mediated through the diversity of their αβ or γδ T cell receptors. Most of the time, γδ T cells do not rely on the recognition of classic HLA molecules, but sense infection or cancer depending more on ubiquitous changes observed across many individuals. Therefore, γδ T cell immune systems can be transferred more easily between individuals. As γδ T cells rapidly recognize ubiquitous changes, γδ T cells are considered to partially belong to the first line of immune defense (the innate immune system), but they also can create immunological memory and therefore are partially adaptive. Each γδ T cell that develops must undergo somatic recombination of its TRG and TRD gene loci to generate a functional γδ TCR surface receptor. These heterodimers, which consist of one TCR γ and one TCR δ chain, are assembled via recombination of the variable (V), diversity (D) and joining (J) gene segments (VDJ recombination) of the TRD locus and, similarly, recombination of the V and J gene segments (VJ recombination) of the TRG locus. Thus, each γδ T cell produces a unique clonal γδ TCR that assembles with CD3 proteins on the cell surface of γδ T cells to transduce activating signals into the cell.

Fig.1 γδ TCR and co-receptor diversity. (Sebestyen, 2020)

Other γδ T Cells Receptors

• Endothelial protein C receptor (EPCR)

A recent report demonstrated a new kind of EPCR-dependent recognition of cytomegalovirus (CMV)-infected cells by γδ T cells. They found that human γδ TCR could directly bound EPCR, which is an MHC-like molecule that binds lipids similar to the antigen-presenting molecule CD1d and can make γδ T cells recognize endothelial cells which are targets for cytomegalovirus infection and epithelial tumors. CMV infection can activate γδ T cells specific for self-antigens inducing by a multimolecular stress signature on the surface of infected cells, containing EPCR and costimulatory ligand (s). The γδ TCR bound EPCR in an antibody-like way, independently of lipids.

• Soluble proteins

Some soluble proteins are also involved in the recognition by γδ T cells, for example, bacterial proteins including the unrelated staphylococcal enterotoxin A (SEA) and the toxin listeriolysin O (LLO). γδ T cells can also recognize heat shock proteins (HSPs), which do not need antigen processing and can occur in the absence of any APCs. There is no substantial evidence demonstrating that HSP recognition involves the TCR. HSPs may signal through TLRs, directly or indirectly through binding peptides or hydrophobic ligands, such as LPS.

• Glycosphingolipid sulfatide

Researches show that the myelin-derived glycosphingolipid sulfatide can also be recognized by human γδ T cells, indicating that there may also exist other kinds of non-peptidic Ags for γδ T cells that have not yet been identified.

Due to the possible advantages of γδ T cell-based immunotherapy, the exploration of γδ T cells receptors is necessary. Creative Biolabs has excellent scientists specialized in γδ T cells and thus provides high-quality γδ T cells receptors services including but not limited to γδ TCR repertoires analysis, γδ TCR transcriptome analysis, γδ TCR generation, and γδ TCR-ligand reaction analysis.

Please feel free to contact us.

Reference

1. Sebestyen, Z.; et al. Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies. Nat Rev Drug Discov. 2020, 19(3): 169-184.