BK polyomavirus Large T antigen peptide-Major Histocompatibility Complex (BKV LTAg pMHC)

BK polyomavirus (BKV) Large T antigen (LTAg) is a multifunctional regulatory protein essential for viral DNA replication and the subversion of host cell cycle control [1]. In BKV-infected cells, LTAg is processed by the proteasome into short peptides that are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules [3]. These peptide-MHC (pMHC) complexes serve as the specific molecular signatures that allow the host's cellular immune system to distinguish infected cells from healthy ones [4]. Recognition of these complexes by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes triggers the release of perforins and granzymes, leading to the apoptosis of the infected cell [2]. In immunocompromised patients, such as kidney transplant recipients, the failure of this immune surveillance leads to BKV reactivation and subsequent BKV-associated nephropathy (BKVAN) [1]. Therapeutic strategies targeting these pMHC complexes include the administration of donor-derived or off-the-shelf virus-specific T cells (VSTs), such as posoleucel [5]. These therapies are designed to provide an exogenous source of T cells that can specifically bind to BKV LTAg pMHC complexes and restore viral control [2]. This targeted approach is highly specific, aiming to minimize damage to the transplanted organ while effectively reducing viral load [1]. Sources: [1] https://pubmed.ncbi.nlm.nih.gov/28630114/ [2] https://pubmed.ncbi.nlm.nih.gov/33513354/ [3] https://www.uniprot.org/uniprotkb/P03071/entry [4] https://pubmed.ncbi.nlm.nih.gov/21832175/ [5] https://clinicaltrials.gov/ct2/show/NCT04390113

Other names

BK virus Large T antigen peptide-HLA complexBKV LTAg-MHCBKV Large T antigen-derived peptide-MHCBKV LTAg pMHC

T-cell receptor-mediated recognition and cytotoxic elimination of infected cells