CD4+ T-cell receptor recognizing Tetanus Toxin Fragment C Domain 1 (DOM) (TCR-DOM)

CD4+ T-cell receptors (TCRs) recognizing the DOM domain are specialized immune receptors that play a pivotal role in the efficacy of DNA fusion vaccines designed for cancer immunotherapy. The DOM domain corresponds to the first domain of the Fragment C of tetanus toxin and contains the highly immunogenic and promiscuous p30 helper epitope (Rice et al., 2001, J Immunol). These TCRs recognize the DOM peptide when it is presented by a variety of MHC Class II alleles, ensuring a broad response across diverse patient populations (King et al., 2004, Hum Gene Ther). In therapeutic applications, the DOM sequence is fused to a tumor-associated antigen, such as WT1 or CEA, within a DNA plasmid. Upon vaccination, the activation of DOM-specific CD4+ T cells provides the essential "help"—including the secretion of Type 1 cytokines like IFN-gamma and IL-2—required to prime and sustain a robust CD8+ cytotoxic T-cell response against the tumor (Ottensmeier et al., 2016, Clin Cancer Res). This strategy effectively bypasses the lack of endogenous T-cell help often seen in cancer patients, thereby enhancing the overall anti-tumor immune response.

Other names

T-cell receptor recognizing p30 epitopeDOM-specific T-cell receptorTetanus toxin Fragment C Domain 1-specific TCRTCR recognizing tetanus toxin helper epitope

Activation of CD4+ helper T cells via MHC Class II presentation of the DOM peptide, leading to cytokine secretion and enhancement of CD8+ T-cell responses.