Adenovirus-derived peptide-Human Leukocyte Antigen complex (Adv-peptide-HLA complex) (Adv-peptide-HLA complex)

The Adenovirus-derived peptide-Human Leukocyte Antigen (HLA) complex is a molecular assembly consisting of a short viral peptide fragment, typically derived from the Adenovirus Hexon protein, bound within the groove of an HLA class I molecule on the surface of infected cells (PubMed: 15126550). This complex serves as the essential recognition unit for the host's cellular immune system, specifically for CD8+ cytotoxic T-lymphocytes (CTLs) via their T-cell receptors (TCRs) (PubMed: 16461632). In clinical settings, particularly for immunocompromised patients such as those undergoing hematopoietic stem cell transplantation, this complex is a critical therapeutic target for adoptive T-cell therapies and TCR-engineered cells designed to restore viral immunity (PubMed: 24661910). The interaction between the TCR and the peptide-HLA complex triggers the destruction of the infected cell, thereby controlling the viral spread (PubMed: 18451253). Understanding the specific HLA alleles, such as HLA-A*01 or HLA-B*07, and the immunodominant peptides involved is vital for the development of precision immunotherapies and vaccines against adenovirus-related pathologies (PubMed: 21148333). Therapeutic strategies often involve the infusion of virus-specific T-cells (VSTs) that have been expanded ex vivo to recognize these specific complexes. Challenges in targeting this complex include viral evasion strategies, such as the downregulation of HLA molecules by the virus to avoid detection. Additionally, ensuring the specificity of the TCR to avoid cross-reactivity with human self-peptides is a primary safety concern in the development of TCR-T therapies.

Other names

Adenoviral peptide-MHC complexAdv-pMHCAdenovirus antigen-HLA complexAdenovirus peptide-major histocompatibility complexAdenovirus hexon peptide-HLA complexAdv-pHLA

The complex acts as a ligand for T-cell receptors (TCRs) on CD8+ cytotoxic T-lymphocytes, triggering intracellular signaling cascades that lead to the release of perforins and granzymes, ultimately resulting in the apoptosis of the adenovirus-infected cell (PubMed: 16461632).