Major Histocompatibility Complex class II-restricted CD4+ T-cell receptor (recognizing VP1-derived peptides) (VP1-specific CD4+ TCR)

Host Major Histocompatibility Complex (MHC) class II-restricted CD4+ T-cell receptors (TCRs) recognizing VP1-derived peptides are specialized immune receptors that play a pivotal role in the surveillance and control of polyomaviruses, most notably the JC virus (JCV) [Jelcic et al., 2015; Berzero et al., 2021]. These TCRs, located on the surface of CD4+ T helper cells, recognize specific peptide fragments of the viral capsid protein 1 (VP1) when they are presented by MHC class II molecules on the surface of antigen-presenting cells [Jelcic et al., 2015; Sellar et al., 2021]. This interaction is fundamental for the activation of adaptive immune responses, including the recruitment of cytotoxic T cells and the production of antiviral cytokines like interferon-gamma [Berzero et al., 2021; Muftuoglu et al., 2018]. In clinical contexts, particularly in patients with compromised immune systems or those receiving certain immunomodulatory therapies, the loss or dysfunction of these VP1-specific CD4+ T cells is a primary driver for the development of Progressive Multifocal Leukoencephalopathy (PML), a debilitating and often fatal demyelinating disease of the central nervous system [Muftuoglu et al., 2018; Cortese et al., 2021]. Consequently, these TCRs are the focus of therapeutic interventions such as adoptive T-cell therapy, where VP1-specific T cells are expanded ex vivo and reinfused into patients to restore viral control [Cortese et al., 2021; Sellar et al., 2021]. They also serve as critical biomarkers for monitoring immune competence and predicting the risk of PML in high-risk populations, such as those with HIV or multiple sclerosis [Lima et al., 2010; Jelcic et al., 2015].

Other names

VP1-specific T-cell receptorJC virus-specific CD4+ T-cell receptorMHC-II restricted VP1 receptorViral capsid protein 1-specific T-cell receptor

Recognition of viral VP1 peptides in the context of MHC class II molecules, triggering CD4+ T-cell activation, cytokine release, and coordination of the antiviral immune response to clear or suppress viral infection [Berzero et al., 2021; Jelcic et al., 2015].