Human leukocyte antigen DQ2.5–T cell receptor complex on gluten-specific CD4+ T cell (HLA-DQ2.5–TCR complex)

The HLA-DQ2.5–TCR complex on gluten-specific CD4+ T cells forms at the immunological synapse where the HLA-DQ2.5 major histocompatibility complex class II molecule, expressed on antigen-presenting cells, displays gluten-derived peptides to the T cell receptor on a subset of CD4+ T cells. This interaction leads to T cell activation and proliferation, constituting the central event in the pathogenesis of celiac disease. Typically, the complex involves HLA-DQ2.5 presenting immunogenic gluten peptides recognized by TCRs with biased usage of specific gene segments (such as TRAV26-1/TRBV7-2). This molecular recognition triggers downstream immune signaling cascades, cytokine release, and resultant tissue damage. Therapeutic targeting focuses on modulating this antigen recognition or T cell activation to manage celiac disease[1][3][7][9].

Other names

HLA-DQ2.5/TCR complexHLA-DQ2.5-gluten–specific TCRHLA-DQ2.5–peptide–TCR complexCD4+ T cell gluten-responsive complexDQ2.5–restricted TCR

Peptide-based inhibitors block gluten peptide presentation or modify TCR recognition. Small molecule disruptors theoretically block TCR-MHC interface signaling. The overall mechanism involves modulation of T cell activation.