MZB1-derived 9-mer peptide presented by HLA-A*02:01 (MZB1/HLA-A*02:01 complex)

The MZB1-derived 9-mer peptide presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) target utilized in advanced cancer immunotherapy. MZB1 (Marginal Zone B and B1 Cell-Specific Protein), also known as pERp1, is an endoplasmic reticulum-resident chaperone essential for immunoglobulin assembly and secretion, particularly in plasma cells [1, 6]. While MZB1 is an intracellular protein, it is processed by the proteasome into short peptides, such as this 9-mer, which are then transported to the cell surface and presented by HLA-A*02:01 molecules [11, 12]. This complex is highly overexpressed in B-cell malignancies, including multiple myeloma and Waldenström macroglobulinemia, making it a selective marker for cancerous plasma cells [8, 10]. Therapeutic strategies targeting this complex involve TCR-like (or TCR-mimic) CAR T-cells, which are engineered to recognize the pMHC complex with high specificity, similar to a natural T-cell receptor but with the potency of a chimeric antigen receptor [11, 13]. This approach is particularly significant as it allows for the targeting of high-abundance intracellular proteins that were previously considered undruggable by conventional surface-targeted antibodies [12].

Other names

MZB1 peptide-MHC complexpERp1-derived peptide/HLA-A*02:01Marginal zone B and B1 cell-specific protein peptide/HLA-A*02:01MZB1-A2 complex

TCR-like CAR T-cell mediated cytotoxicity via specific recognition of the MZB1 peptide-HLA-A*02:01 complex on the cell surface, leading to targeted lysis of malignant cells.