Human leukocyte antigen–T cell receptor interface (HLA–TCR interface)

The **human leukocyte antigen–T cell receptor (HLA–TCR) interface** refers to the molecular contact region between an HLA molecule (also known as a major histocompatibility complex, or MHC, in humans) on an antigen-presenting cell and the T cell receptor (TCR) on a T lymphocyte. This interface is not itself a molecular entity, but rather the crucial site where TCRs recognize peptides presented by the HLA molecule, enabling activation of T cells and the adaptive immune response[1][2][6]. This interaction is governed by the structural alignment and molecular complementarity between the peptide-HLA complex and the TCR, with specificity determined by contacts between the TCR's complementarity-determining regions (CDRs) and both the presented peptide and the HLA molecule itself[1][2][4]. The HLA–TCR interface is fundamental to antigen-specific T cell responses and influences outcomes in autoimmunity, infection, cancer immunosurveillance, and immunotherapies. However, the interface itself is not a discrete gene, protein, or canonical drug target. Some therapies engineer TCRs or modify antigens to manipulate this recognition event (e.g., TCR-T or CAR-T therapies)[4][6], but drugs do not target the interface directly as a stand-alone molecular entity. Notes on correctness: "**HLA–TCR interface**" names a structural and functional region important in immunology, but does not correspond to a unique molecule, protein, gene, receptor, or enzyme. It is a concept describing the physical interactions between two separate protein complexes. Thus, it is not a canonical therapeutic target and some information fields do not apply.