T-cell receptor recognizing VP1-derived peptides presented on MHC class II (TCR-VP1-MHCII)

T-cell receptors (TCRs) recognizing VP1-derived peptides presented on MHC class II molecules are specialized immune receptors that mediate the recognition of polyomaviruses, including BK virus (BKV) and JC virus (JCV). The VP1 protein is the major structural component of the viral capsid and contains highly immunogenic epitopes that are processed and presented by MHC class II molecules, such as HLA-DR, to CD4+ T cells (Leboeuf et al., 2017). These TCRs play a pivotal role in controlling viral latency and preventing reactivation in healthy individuals. However, in the context of immunosuppression—such as following hematopoietic stem cell or solid organ transplantation—the absence or dysfunction of these VP1-specific T cells can lead to severe diseases like BK virus-associated nephropathy (BKVAN) or progressive multifocal leukoencephalopathy (PML) (Yousef et al., 2021). Therapeutic interventions targeting this pathway include adoptive T-cell therapy using virus-specific T cells (VSTs) and the development of TCR-engineered T cells (TCR-T) designed to restore specific cellular immunity against the virus (Papadopoulou et al., 2014). These therapies work by introducing T cells equipped with high-affinity TCRs that recognize the VP1-MHC II complex, thereby triggering an effector immune response to eliminate infected cells (Mueller et al., 2021).

Other names

VP1-specific T-cell receptorMHC class II-restricted VP1-specific TCRPolyomavirus VP1-specific TCRBKV-specific T-cell receptorJCV-specific T-cell receptor

Recognition of viral VP1 peptides presented by MHC class II molecules on the surface of infected or antigen-presenting cells, leading to T-cell activation, proliferation, and the release of effector cytokines to control viral replication.