Human leukocyte antigen A*02:01–B-cell maturation antigen-derived peptide complex (HLA-A*02:01–BCMA)

The HLA-A*02:01–BCMA-derived peptide complex is a peptide-major histocompatibility complex (pMHC) consisting of the human leukocyte antigen (HLA) allele A*02:01 and a peptide fragment derived from the B-cell maturation antigen (BCMA, also known as TNFRSF17) (Bae et al., 2020). BCMA is a transmembrane protein primarily expressed on the surface of mature B lymphocytes and plasma cells, and it is highly overexpressed in multiple myeloma (MM) and other B-cell malignancies (Bae et al., 2019). The presentation of BCMA-derived peptides, such as the immunogenic BCMA72-80 (native sequence VLMFLLRKI or heteroclitic YLMFLLRKI), by HLA-A*02:01 allows for the recognition of tumor cells by CD8+ cytotoxic T lymphocytes (CTLs) (Bae et al., 2020). This complex serves as a critical therapeutic target for various immunotherapies, including peptide-based vaccines, T-cell receptor-engineered T-cell (TCR-T) therapies, and TCR-like antibodies (Bae et al., 2019; Maroto-Martin et al., 2025). These therapies aim to exploit the high specificity of the pMHC complex to selectively eliminate malignant plasma cells while sparing most healthy tissues, although challenges such as antigen escape and HLA restriction remain (Bae et al., 2020; Letouzé et al., 2024). Research has shown that heteroclitic variants of these peptides can enhance binding affinity and stability, leading to more robust and durable T-cell responses in patients (Bae et al., 2020).

Other names

HLA-A*02:01–BCMA72-80 complexBCMA-HLA-A*02:01 complexBCMA-pMHC complexHLA-A*02:01–TNFRSF17 peptide complexHLA-A*02:01–BCMA54-62 complex

Recognition of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce targeted lysis of BCMA-expressing malignant cells.