Merkel cell polyomavirus large and small T antigen–derived peptides presented on MHC class I (MCPyV T-Ag pMHC-I)

Merkel cell polyomavirus (MCPyV) large and small T antigen–derived peptides presented on MHC class I represent a critical class of tumor-specific antigens in Merkel cell carcinoma (MCC). In approximately 80% of MCC cases, the virus integrates into the host genome, resulting in the continuous expression of viral oncoproteins that are essential for maintaining the malignant phenotype (1.1.2, 1.3.3). These proteins are processed by the proteasome and presented as short peptides on the cell surface by Major Histocompatibility Complex (MHC) class I molecules (1.2.3, 1.3.1). Because these viral antigens are absent in healthy tissues, they serve as highly specific targets for immunotherapies, including TCR-engineered T cells (e.g., AFNT-211) and therapeutic DNA vaccines like ITI-3000 (1.1.1, 1.1.2). Targeting these pMHC complexes aims to bypass the immunosuppressive tumor microenvironment and induce a potent, lytic CD8+ T-cell response (1.4.1, 1.4.2). However, therapeutic efficacy can be challenged by tumor-mediated downregulation of MHC class I expression, which is a common mechanism of immune evasion in MCC (1.3.3).

Other names

MCPyV T-antigen epitopesMerkel cell polyomavirus oncoprotein-derived peptidesMCPyV T-Ag HLA-I complexesMCPyV LT/sT MHC-I peptidesMerkel cell polyomavirus T-antigen peptide:HLA complex

Direct recognition of the peptide-MHC complex by engineered or endogenous T-cell receptors (TCRs) to induce cytotoxic cell death of tumor cells; therapeutic vaccines induce endogenous T-cell expansion against these specific epitopes.