T cell receptor recognizing citrullinated alpha-enolase (ENO1) peptide–MHC class II complex (TCR-citENO1-MHCII)

The T cell receptor (TCR) on CD4+ T cells that recognizes citrullinated alpha-enolase (ENO1) peptides presented by MHC class II molecules is a pivotal mediator of immune responses to post-translationally modified antigens. Citrullination, the enzymatic conversion of arginine to citrulline by peptidylarginine deiminases (PADs), creates neoepitopes that can bypass central tolerance and trigger potent immune responses. In autoimmune conditions like rheumatoid arthritis (RA), these TCRs are central to pathogenesis, as they recognize citrullinated ENO1 (specifically the CEP-1 epitope) presented by HLA-DRB1*04:01, leading to the activation of inflammatory Th17 and Th1 cells (Cook et al., 2014). In the field of oncology, this mechanism is being harnessed for cancer immunotherapy, as many tumors overexpress citrullinated proteins due to cellular stress and nutrient deprivation. Therapeutic vaccines such as Modi-1 (Scancell) aim to stimulate these specific CD4+ T cell receptors to induce a direct anti-tumor effect, leveraging the high density of MHC class II-presented citrullinated peptides on the surface of cancer cells (Brentville et al., 2020). This target represents a novel class of "moditopes" that allow the immune system to distinguish stressed malignant cells from healthy tissue. By targeting these TCRs, clinicians hope to bypass the limitations of traditional MHC class I-restricted therapies, which are often hindered by tumor-mediated HLA downregulation.

Other names

Citrullinated enolase-specific T-cell receptorAnti-cit-ENO1 TCRCD4+ TCR specific for citrullinated alpha-enolaseTCR recognizing citrullinated ENO1

Activation of antigen-specific CD4+ T cells through the recognition of citrullinated ENO1 peptides presented on MHC class II molecules, inducing a Th1-polarized immune response.