Human leukocyte antigen class I molecules presenting chronic lymphocytic leukemia-associated peptides (HLA-I/CLL-peptide complex)

Human leukocyte antigen (HLA) class I molecules presenting chronic lymphocytic leukemia (CLL)-associated peptides are cell-surface complexes that play a critical role in the immune recognition of malignant B cells. These complexes consist of an HLA heavy chain, beta-2 microglobulin, and a short peptide fragment derived from proteins that are overexpressed or mutated in CLL, such as ROR1, MDM2, or PRAME (PubMed: 24121463). By presenting these intracellularly derived antigens to the immune system, the complexes allow CD8+ cytotoxic T cells to identify and eliminate leukemic cells via T-cell receptor (TCR) binding (PubMed: 31534003). In clinical development, these peptide-HLA (pHLA) complexes are targeted by TCR-engineered T cells and therapeutic vaccines to provide a highly specific anti-tumor response (PubMed: 27137445). However, the effectiveness of these therapies can be limited by tumor-mediated HLA downregulation or the risk of off-target toxicity if the targeted peptide is also presented on essential healthy tissues (PubMed: 29038257).

Other names

MHC class I CLL-associated peptide complexesCLL-specific peptide-HLA complexesHLA-I/CLL-antigen complexesCLL immunopeptidomepHLA-CLL

Binding of therapeutic T-cell receptors (TCRs) or TCR-like antibodies to the peptide-HLA complex, leading to the activation of cytotoxic T-cell signaling and subsequent lysis of the target leukemic cell (PubMed: 31534003).