Probable non-functional T cell receptor gamma variable
1_MRWAL 6_ AVLLA 11_ FLSPA 16_ SQISS 21_ NLEGR 26_ TKSVT 31_ RLTGS 36_ SAEIT 41_ CDLPG 46_ ASTLY 51_ IHWYL 56_ HQEGK 61_ APQCL 66_ LYYEP 71_ YYSRV 76_ VLESG 81_ ITPGK 86_ YDTGS 91_ TRSNW 96_ NLRLQ 101_ NLIKN 106_ DSGFY 111_YCATW
1: Probable non-functional open reading frame (ORF) of V region of the variable domain of T cell receptor (TR) gamma chain (PubMed:24600447). Non-functional ORF generally cannot participate in the synthesis of a productive T cell receptor (TR) chain due to altered V-(D)-J or switch recombination and/or splicing site (at mRNA level) and/or conserved amino acid change (protein level) (PubMed:9619395). 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)