HLA-A*02:01-HM1.24 peptide complex (HLA-A2/HM1.24)

The HLA-A*02:01-HM1.24 peptide complex is a therapeutic target primarily relevant in the treatment of multiple myeloma. HM1.24, also known as BST2 or CD317, is a type II transmembrane glycoprotein that is highly overexpressed on malignant plasma cells, making it a specific marker for myeloma (UniProt Q10589). The target specifically involves the presentation of an HM1.24-derived epitope (typically the 126-134 sequence: KLQDASAEV) by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule. This complex is of particular interest in immunotherapy because it has been identified as a cross-reactive target for T cells originally specific to the Melan-A/MART-1 melanoma antigen analog (ELAGIGILTV). This molecular mimicry allows for the redirection of established Melan-A-targeted T-cell receptors to recognize and eliminate multiple myeloma cells (Poschke et al., 2012, PubMed: 22492964). By leveraging this cross-reactivity, researchers can utilize potent TCR-based strategies to induce cytotoxic T-lymphocyte responses against plasma cell malignancies that express the HM1.24 antigen.

Other names

BST2 peptide-HLA-A*02:01 complexCD317 peptide-HLA-A*02:01 complexHM1.24(126-134)-HLA-A*02:01Bone marrow stromal cell antigen 2 peptide-MHC complex

The target is recognized by T-cell receptors (TCRs) that are cross-reactive between the Melan-A/MART-1 analog peptide and the HM1.24-derived peptide. Upon binding, the T cell is activated, leading to the release of perforins and granzymes, which induces apoptosis in the HM1.24-expressing target cell (e.g., multiple myeloma cells).