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Hepatitis B surface antigen-derived peptide–Major Histocompatibility Complex class I complex (HBsAg-pMHC I) (HBsAg-pMHC I)

Target
HBsAg-pMHC I
Molecular classification
Antigen-MHC complex, Protein-peptide complex
01

Overview

The Hepatitis B surface antigen-derived peptide–Major Histocompatibility Complex class I complex (HBsAg-pMHC I) is a molecular assembly consisting of a specific peptide fragment from the HBsAg protein bound within the groove of an MHC class I molecule (Maini & Pallett, 2018, PMID: 29433956). This complex is presented on the surface of hepatocytes in patients with chronic Hepatitis B virus (HBV) infection and on hepatocellular carcinoma (HCC) cells that have integrated HBV DNA (Qiao et al., 2021, PMID: 33613465). It serves as the primary recognition element for CD8+ T-cell receptors (TCRs), which initiate a cytotoxic immune response to destroy the target cell. In chronic infection, the natural T-cell response against this complex is often exhausted or absent, leading to viral persistence and oncogenesis. Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies, such as SCG101 and LioCyx-M, which provide patients with synthetic T cells capable of recognizing these specific viral markers (SCG Cell Therapy, 2023; Lion TCR, 2022). These treatments aim to achieve functional cure in CHB or tumor regression in HBV-related HCC. Key challenges include the requirement for specific HLA matching (e.g., HLA-A*02:01) and the management of potential liver inflammation or cytokine release syndrome following T-cell activation.

Other names
HBsAg-HLA complexHBV surface antigen peptide-MHC IHBsAg-pMHCHBV-specific pMHCHBsAg-derived peptide–MHC I complexes recognized by CD8+ T cell receptors
02

Mechanism of action

T-cell receptor-mediated recognition of viral epitopes presented on MHC I, leading to directed cytotoxic T-cell activation and lysis of target cells.

03

Biological functions

Antigen presentationImmune responseT-cell activationCytolysis
04

Disease associations

InfectionCancer
05

Safety considerations

Cytokine release syndrome (CRS)On-target off-tumor toxicityHepatotoxicity (liver flare)Neurotoxicity
06

Interacting drugs

SCG101

2 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeHBsAg expressionHBV DNA levelsSerum HBsAg quantification

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