Signaling lymphocytic activation molecule family member 7-derived peptide-HLA-A*02:01-T-cell receptor complex (SLAMF7-HLA-A2-TCR complex)

The SLAMF7-derived HLA-A2 peptide / TCR complex is a molecular assembly consisting of a specific immunogenic peptide from the Signaling Lymphocytic Activation Molecule Family member 7 (SLAMF7) protein, the Human Leukocyte Antigen (HLA)-A*02:01 molecule, and a cognate T-cell receptor (TCR). SLAMF7, also known as CS1 or CD319, is a cell surface glycoprotein that is highly and nearly universally expressed on malignant plasma cells in multiple myeloma, while showing restricted expression on normal lymphocytes (Bae et al., 2012, PubMed: 22515233). In this complex, the HLA-A2 molecule presents intracellularly processed SLAMF7 peptides, such as the LLVPATVAA (232–240) epitope, to the surface for recognition by CD8+ T-cells (Tai et al., 2008, PubMed: 18042804). This interaction is the fundamental target for TCR-engineered T-cell (TCR-T) therapies, which are designed to redirect the immune system to specifically kill myeloma cells. Unlike monoclonal antibodies that target the native surface protein, TCR-based approaches targeting this complex can potentially recognize epitopes derived from various protein domains presented via the MHC pathway. The formation of this complex triggers a signaling cascade within the T-cell, resulting in the directed release of cytotoxic granules and the induction of apoptosis in the SLAMF7-presenting cell (Gogishvili et al., 2017, PubMed: 28655776). Therapeutic development focusing on this complex must manage potential 'fratricide' effects, as SLAMF7 is also expressed on the therapeutic T-cells themselves.

Other names

CS1-HLA-A2-TCR complexCD319-HLA-A2-TCR complexSLAMF7-MHC-TCR complexSLAMF7(232–240)-HLA-A2-TCR complex

T-cell receptor-mediated recognition of the SLAMF7 peptide presented by HLA-A*02:01, leading to T-cell activation, secretion of perforins and granzymes, and subsequent lysis of the target cell.