Cathepsin G-derived peptide–HLA-A*02:01 complex (CTSG-peptide-HLA complex)

The Cathepsin G-derived peptide–HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of leukemic cells, particularly in Acute Myeloid Leukemia (AML) (Blood, 2016, 128:2532). Cathepsin G (CTSG) is a serine protease normally stored in the azurophil granules of neutrophils but is aberrantly overexpressed or processed in myeloid leukemia blasts (Journal of Clinical Investigation, 2019, 129:2475). A specific 9- or 10-amino acid peptide, most notably the CG1 peptide (sequence: RLLMRTFNYV), derived from CTSG is presented by the HLA-A*02:01 molecule, making it a highly specific target for T-cell-based immunotherapies (NexImmune, 2021). Because CTSG expression is largely restricted to the myeloid lineage, this complex serves as a tumor-associated antigen that can be targeted by T-cell receptor (TCR) engineered T cells, peptide vaccines, or artificial immune modulatory systems. Therapeutic strategies aim to exploit the differential expression between leukemic blasts and healthy non-myeloid tissues to induce a potent anti-leukemic immune response. However, since normal neutrophils also express Cathepsin G, monitoring for myeloid toxicity and severe neutropenia is a critical safety consideration in clinical development (Frontiers in Immunology, 2020, 11:584).

Other names

CG1-HLA-A*02:01 complexCathepsin G peptide-MHC complexCTSG-HLA-A2CG1-HLA-A2 complexCathepsin G (CG1) peptide-HLA-A*02:01

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and selective lysis of leukemia cells expressing the antigen.