Beta-2-microglobulin (B2M) genomic DNA locus (B2M)

The Beta-2-microglobulin (B2M) genomic DNA locus encodes the light chain of the Major Histocompatibility Complex (MHC) class I molecule. This locus is essential for the assembly and stable cell-surface expression of all MHC class I proteins, which are required for presenting intracellular antigens to CD8+ T cells (UniProt P61769). In the context of modern immunotherapy, the B2M locus is a primary target for gene-editing technologies like CRISPR/Cas9 to create universal, off-the-shelf allogeneic CAR-T cells (PubMed: 28803738). By disrupting this locus, researchers can eliminate HLA expression to avoid host-versus-graft rejection in patients. However, loss-of-function mutations in the B2M locus are frequently observed in various cancers, where they facilitate immune evasion by preventing the presentation of neoantigens (PubMed: 30249024). Additionally, the B2M protein is involved in iron homeostasis through its interaction with the HFE protein (NCBI Gene: 567). Its accumulation in patients with chronic kidney disease leads to dialysis-related amyloidosis, where the protein forms pathogenic fibrils. Therapeutic interventions targeting this locus aim to either restore immune recognition in cancer or engineer immune-silent cells for transplantation.

Other names

B2MBeta-2-microglobulinCDABP0092Hdcma22p

Gene knockout via CRISPR/Cas9 or other site-specific nucleases to eliminate surface expression of MHC class I molecules.