Human herpesvirus 6-infected cells presenting HHV-6 peptides on human leukocyte antigen molecules (HHV-6-peptide-HLA complex)

Human herpesvirus 6 (HHV-6)-infected cells presenting viral peptides on human leukocyte antigen (HLA) molecules are a primary target for cellular immunotherapies, particularly in immunocompromised patients (Zerr et al., 2005, Blood). HHV-6 is a ubiquitous beta-herpesvirus that remains latent in the host after primary infection but can reactivate following hematopoietic stem cell or solid organ transplantation, leading to severe complications such as encephalitis and pneumonitis (Tzannou et al., 2017, Journal of Clinical Oncology). The target complex is formed when viral proteins, such as the U54 tegument protein or U90 immediate-early protein, are proteolytically processed into peptides and loaded onto HLA Class I or II molecules for surface display (Gerdemann et al., 2013, Blood). Therapeutic strategies, such as virus-specific T-cell (VST) therapy, utilize T-cell receptors to specifically recognize these peptide-MHC complexes, triggering the destruction of the infected cell and the release of antiviral cytokines. This approach aims to restore viral immunity and control infection without the broad toxicity associated with traditional antiviral drugs like ganciclovir or foscarnet. Challenges in targeting this complex include the high polymorphism of HLA molecules and the potential for viral escape through the downregulation of antigen presentation machinery.

Other names

HHV-6 peptide-MHC complexHHV-6 pMHCHHV-6-infected cellsHHV-6 antigen-presenting cellsHHV-6-specific HLA-peptide complex

T-cell receptor-mediated recognition of viral peptides presented on HLA molecules, leading to cytotoxic T lymphocyte activation and lysis of infected cells.