背景
TCR delta (T cell receptor delta chain) is one of the heterodimeric component chains of the γδ T cell receptor (TCR), covalently linked to the gamma chain via disulfide bonds to form the unique TCRγδ complex, playing an important immune surveillance role at the interface between innate and adaptive immunity. The structure of this protein consists of a variable region (Vδ), diversity region (Dδ), joining region (Jδ), and constant region (Cδ), with its gene locus located within the TCRα/δ locus (on human chromosome 14), generating an extremely diverse antigen recognition repertoire through somatic V(D)J gene recombination. Unlike conventional αβ T cells that recognize MHC-peptide complexes, the TCR delta chain endows γδ T cells with the ability to recognize non-classical antigens, including phosphoantigens, lipid molecules, stress-induced proteins (such as MICA/MICB, ULBP), and unprocessed small-molecule pyrophosphates. This recognition mode does not depend on MHC presentation, enabling γδ T cells to rapidly respond to pathogen infections and tumor-transformed cells. γδ T cells expressing specific TCR delta chains (particularly Vδ1, Vδ2, and Vδ3 subtypes) play critical roles in tissue-resident immunity, epithelial barrier maintenance, and tumor surveillance. Among these, the predominant Vγ9Vδ2 T cells in human peripheral blood specifically recognize microbial-derived pyrophosphate antigens (such as (E)-4-hydroxy-3-methyl-2-butenyl pyrophosphate) through the Vδ2 region of their TCR delta chain, leading to rapid activation in anti-infective immunity. Clinical studies have shown that γδ T cells infiltrating the tumor microenvironment exert direct cytotoxic effects or assist other immune cells through TCR delta chain-mediated recognition. Downregulation or functional deficiency of the TCR delta chain is associated with immune evasion and poor prognosis in various solid tumors (such as colorectal cancer, breast cancer, and melanoma), making immunocellular therapies based on γδ T cells (particularly those involving engineered TCR delta chain modifications) an emerging research direction in the field of cancer therapy.