Major histocompatibility complex class I molecules presenting VP1-derived peptides (MHC-I/VP1)

Major histocompatibility complex class I (MHC-I) molecules presenting VP1-derived peptides are specialized molecular complexes that serve as the primary recognition signal for the adaptive immune system to detect polyomavirus infections [UniProt P03089]. VP1 is the major capsid protein of viruses such as the JC virus (JCV) and BK virus (BKV), and its intracellular processing results in short peptides that are loaded onto MHC-I molecules for surface display [Cortese et al., 2021]. This peptide-MHC (pMHC) complex is specifically targeted by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which initiate a cascade leading to the destruction of the infected cell [Muftuoglu et al., 2018]. In clinical practice, this complex is a critical target for adoptive immunotherapies, such as virus-specific T cells (VSTs) and TCR-engineered T cells, designed to treat Progressive Multifocal Leukoencephalopathy (PML) and BK virus-associated nephropathy [ClinicalTrials.gov NCT04605484]. The therapeutic efficacy of targeting this complex depends heavily on the specific HLA allele of the patient, most commonly HLA-A*02:01, which determines the repertoire of presented VP1 peptides. Potential challenges in targeting this complex include viral mutations that lead to immune escape and the risk of cross-reactivity with self-antigens, which can cause off-target inflammatory responses.

Other names

HLA-VP1 complexMHC-I/VP1 peptide complexpMHC complexVP1-MHC class I complexHLA-A*02:01-restricted VP1 peptide complex

The complex acts as a specific ligand for T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, triggering the release of perforins and granzymes to induce apoptosis in infected cells.