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Adenoviral peptide-Human Leukocyte Antigen (HLA) complex (Adv-pHLA)

Target
Adv-pHLA
Molecular classification
Peptide-MHC complex, Antigen-presenting complex, MHC Class I, Cellular target
01

Overview

The Adenoviral peptide-Human Leukocyte Antigen (HLA) complex is the primary immunological target found on the surface of host cells infected with adenovirus (Leen et al., 2006, Nature Medicine). This complex consists of a short viral peptide, often derived from the highly conserved hexon or penton proteins, non-covalently bound to the groove of an MHC Class I molecule (Feuchtinger et al., 2008, Blood). Its biological function is to signal the presence of intracellular viral infection to the adaptive immune system, specifically to CD8+ cytotoxic T lymphocytes (UniProt, 2024). In patients with weakened immune systems, such as those post-hematopoietic stem cell transplant, the failure to recognize these complexes leads to disseminated and often fatal infection (AlloVir, 2023). Therapeutic interventions like posoleucel utilize virus-specific T cells (VSTs) that are engineered or selected to bind these specific pHLA complexes with high affinity. Upon binding, the T cells release cytotoxic granules containing perforin and granzymes, which trigger apoptosis in the infected host cell (PubMed, 2022). This target is highly specific to infected cells, which helps in reducing the risk of systemic toxicity compared to broad-spectrum antivirals. Monitoring the clearance of cells presenting these complexes is typically done by measuring viral DNA levels in the blood.

Other names
Adenovirus-specific peptide-MHC complexAdv-pMHCAdenoviral antigen-HLA complexAdenovirus-infected cell surface antigensAdenovirus-infected host cells
02

Mechanism of action

Recognition of the viral peptide-HLA complex by the T-cell receptor (TCR) of cytotoxic T lymphocytes, leading to targeted cell lysis via the perforin/granzyme pathway (Leen et al., 2006, Nature Medicine).

03

Biological functions

Antigen presentationImmune responseT-cell activationApoptosis inductionViral replication control
04

Disease associations

Adenovirus infectionInfection in immunocompromised hostsViral pneumoniaHemorrhagic cystitis
05

Safety considerations

Graft-versus-host disease (GvHD) (AlloVir, 2023)Cytokine release syndrome (CRS)Off-target cross-reactivity with self-peptides (PubMed, 2022)
06

Interacting drugs

Posoleucel (ALVR106)

2 more in the full profile.

07

Biomarkers

HLA typing (e.g., HLA-A*02:01)Adenoviral DNA load (qPCR)Hexon-specific T-cell frequency

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