CD4+ T-cell receptor recognizing Merkel cell polyomavirus large T antigen-derived peptide presented on MHC class II (MCPyV LT-specific CD4+ TCR)

The CD4+ T-cell receptor (TCR) recognizing Merkel cell polyomavirus (MCPyV) Large T (LT) antigen-derived peptides presented on MHC class II is a specialized immune receptor utilized in the development of adoptive T-cell therapies for Merkel cell carcinoma (MCC) (Paulson et al., 2018, Nature Communications). MCPyV is a double-stranded DNA virus integrated into the genome of approximately 80% of MCC tumors, where it constitutively expresses the LT antigen, a viral oncogene essential for tumor survival (Church et al., 2018, Clinical Cancer Research). Because the LT antigen is a foreign viral protein not found in healthy human tissues, it serves as a highly specific neoantigen for immunotherapy. CD4+ TCRs specific for this antigen recognize peptide fragments presented by MHC class II molecules, such as HLA-DR, on the surface of tumor cells or antigen-presenting cells within the tumor microenvironment (Jing et al., 2016, Journal of Investigative Dermatology). Upon binding, these TCRs trigger T-cell activation, leading to the secretion of pro-inflammatory cytokines like IFN-gamma and TNF-alpha, which can orchestrate a broader immune response and exert direct cytotoxic effects against the tumor. Therapeutic strategies involve engineering a patient's own T cells to express these specific TCRs (TCR-T therapy) to enhance the immune system's ability to eradicate MCPyV-positive MCC (Nghiem et al., 2016, NEJM). This target is particularly valuable for patients with advanced MCC who have failed standard checkpoint inhibitor therapies.

Other names

MCPyV-specific TCRMerkel cell polyomavirus Large T antigen-specific T-cell receptorHLA-II restricted MCPyV TCRLT-specific CD4+ TCRMCPyV-targeted T-cell receptor

Engineered T cells expressing this specific TCR recognize Merkel cell polyomavirus Large T antigen peptides presented by MHC class II molecules on tumor cells, triggering T-cell activation, cytokine release, and direct tumor cell lysis.