Merkel cell polyomavirus T-antigen peptide presented by HLA-A*02:01 (MCPyV T-antigen/HLA-A*02:01)

The Merkel cell polyomavirus (MCPyV) T-antigen peptide presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) found on the surface of Merkel cell carcinoma (MCC) cells (Feng et al., 2008, Science). MCPyV is integrated into the host genome in approximately 80% of MCC cases, leading to the constitutive expression of viral oncoproteins, specifically the Large T (LT) and Small T (sT) antigens (Iyer et al., 2011, Clin Cancer Res). These antigens are required for tumor cell survival and proliferation, making them ideal targets for therapy. Because these viral proteins are not expressed in healthy human tissues, they serve as highly specific tumor-associated antigens (Koelle et al., 2017, Curr Opin Virol). The HLA-A*02:01 allele is one of the most common MHC class I molecules and presents immunodominant peptides, such as the LT-derived KLLEIAPNC sequence, to the immune system (Iyer et al., 2011). Therapeutic strategies targeting this complex primarily involve adoptive cell therapies, such as T-cell receptor (TCR) engineered T cells like KITE-367 (Kite Pharma Pipeline). These TCR-T cells are designed to recognize the pMHC and induce a potent cytotoxic immune response against the cancer cells. This target is particularly attractive because the viral origin of the peptide minimizes the risk of central tolerance and off-target effects on normal tissues. However, therapeutic challenges include immune escape via HLA downregulation and the potential for cytokine release syndrome (Church et al., 2018, Cancer Immunol Res).

Other names

MCPyV LT-antigen/HLA-A*02:01MCPyV sT-antigen/HLA-A*02:01KLLEIAPNC/HLA-A*02:01 complexMerkel cell polyomavirus oncoprotein peptide-MHC complex

T-cell receptor (TCR) mediated recognition and cytotoxic T-lymphocyte (CTL) activation