Leukemia-associated antigen presented on Major Histocompatibility Complex (LAA-MHC)

Leukemia-associated antigens (LAAs) are proteins or peptides derived from intracellular proteins that are overexpressed or mutated in leukemic cells and subsequently presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Anguille et al., 2012). These peptide-MHC (pMHC) complexes serve as critical targets for the adaptive immune system, particularly CD8+ cytotoxic T lymphocytes, which recognize them via T-cell receptors (TCRs) (Schmitt et al., 2009). Common examples of LAAs include Wilms Tumor 1 (WT1), Preferentially Expressed Antigen in Melanoma (PRAME), and Proteinase 3 (PR3) (Greiner et al., 2006). In therapeutic contexts, these antigens are targeted using various modalities such as peptide vaccines, TCR-engineered T-cell (TCR-T) therapies, and TCR-like antibodies (SELLAS Life Sciences, 2024; Medigene AG, 2023). The primary challenge in targeting LAAs is ensuring high specificity to avoid off-target toxicities, as many LAAs are also expressed at low levels in normal tissues. Additionally, leukemic cells may employ immune escape mechanisms such as the downregulation of MHC molecules to avoid detection (Anguille et al., 2012).

Other names

Leukemia-associated antigenLAATumor-associated antigen in leukemiapMHC complexLeukemia neoantigenMinor histocompatibility antigen

Induction of antigen-specific T-cell responses or direct targeting of peptide-MHC complexes to trigger T-cell mediated lysis of leukemic cells (Schmitt et al., 2009; Anguille et al., 2012).