Leukemia-associated antigen presented on MHC molecules (LAA-MHC)

Leukemia-associated antigens (LAAs) presented on MHC molecules are short peptide sequences derived from intracellular proteins that are overexpressed or mutated in leukemia cells. These peptides are processed by the proteasome and loaded onto Major Histocompatibility Complex (MHC) molecules, typically Class I, for presentation on the cell surface to cytotoxic T lymphocytes [1][2]. This mechanism allows the immune system to detect internal cellular abnormalities that are not visible via surface proteins. Prominent LAAs include Wilms Tumor 1 (WT1), PRAME, and Proteinase 3, which are highly relevant in diseases like Acute Myeloid Leukemia (AML) [3]. Therapeutic interventions targeting these complexes include peptide vaccines, such as Galinpepimut-S, and TCR-engineered T-cell therapies, which are designed to recognize the specific peptide-MHC ligand with high specificity [4]. Despite their potential, challenges include the risk of off-target toxicity if the peptide is presented by healthy tissues and the potential for tumor escape through the downregulation of MHC molecules [5]. [1] Kessler JH, Melief CJ. (2007). Leukemia. [2] Stevanović S, et al. (2007). Leukemia. [3] Greiner J, et al. (2006). Blood. [4] Schmitt A, et al. (2009). Blood. [5] Dhatchinamoorthy K, et al. (2021). Frontiers in Immunology.

Other names

HLA-presented leukemia antigensLeukemia-associated peptide-MHC complexesTumor-associated antigens in leukemiaLAA-HLA complexesMHC-restricted leukemia antigens

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, inducing cytotoxic T-lymphocyte (CTL) activation and subsequent apoptosis of the leukemia cell.