7ryl

Structural highlights

Function

TRBC1_HUMAN TRGV4_HUMAN V region of the variable domain of T cell receptor (TR) gamma chain that participates in the antigen recognition (PubMed:24600447). Gamma-delta TRs recognize a variety of self and foreign non-peptide antigens frequently expressed at the epithelial boundaries between the host and external environment, including endogenous lipids presented by MH-like protein CD1D and phosphoantigens presented by butyrophilin-like molecule BTN3A1. Upon antigen recognition induces rapid, innate-like immune responses involved in pathogen clearance and tissue repair (PubMed:23348415, PubMed:28920588). Binding of gamma-delta TR complex to antigen triggers phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the CD3 chains by the LCK and FYN kinases, allowing the recruitment, phosphorylation, and activation of ZAP70 that facilitates phosphorylation of the scaffolding proteins LCP2 and LAT. This lead to the formation of a supramolecular signalosome that recruits the phospholipase PLCG1, resulting in calcium mobilization and ERK activation, ultimately leading to T cell expansion and differentiation into effector cells (PubMed:25674089). Gamma-delta TRs are produced through somatic rearrangement of a limited repertoire of variable (V), diversity (D), and joining (J) genes. The potential diversity of gamma-delta TRs is conferred by the unique ability to rearrange (D) genes in tandem and to utilize all three reading frames. The combinatorial diversity is considerably increased by the sequence exonuclease trimming and random nucleotide (N) region additions which occur during the V-(D)-J rearrangements (PubMed:24387714).^{[1] [2] [3] [4] [5]}

References

1. ↑ Vantourout P, Hayday A. Six-of-the-best: unique contributions of gammadelta T cells to immunology. Nat Rev Immunol. 2013 Feb;13(2):88-100. doi: 10.1038/nri3384. PMID:23348415 doi:http://dx.doi.org/10.1038/nri3384
2. ↑ Chien YH, Meyer C, Bonneville M. gammadelta T cells: first line of defense and beyond. Annu Rev Immunol. 2014;32:121-55. doi: 10.1146/annurev-immunol-032713-120216., Epub 2014 Jan 2. PMID:24387714 doi:http://dx.doi.org/10.1146/annurev-immunol-032713-120216
3. ↑ Lefranc MP. Immunoglobulin and T Cell Receptor Genes: IMGT((R)) and the Birth and Rise of Immunoinformatics. Front Immunol. 2014 Feb 5;5:22. doi: 10.3389/fimmu.2014.00022. eCollection 2014. PMID:24600447 doi:http://dx.doi.org/10.3389/fimmu.2014.00022
4. ↑ Ribeiro ST, Ribot JC, Silva-Santos B. Five Layers of Receptor Signaling in gammadelta T-Cell Differentiation and Activation. Front Immunol. 2015 Jan 26;6:15. doi: 10.3389/fimmu.2015.00015. eCollection 2015. PMID:25674089 doi:http://dx.doi.org/10.3389/fimmu.2015.00015
5. ↑ Nielsen MM, Witherden DA, Havran WL. gammadelta T cells in homeostasis and host defence of epithelial barrier tissues. Nat Rev Immunol. 2017 Dec;17(12):733-745. doi: 10.1038/nri.2017.101. Epub 2017, Sep 18. PMID:28920588 doi:http://dx.doi.org/10.1038/nri.2017.101