Beta-2-microglobulin (B2M) (B2M)

Beta-2-microglobulin (B2M) is a 12 kDa protein that serves as the invariant light chain of the Major Histocompatibility Complex (MHC) Class I molecule, which is expressed on the surface of nearly all nucleated cells (UniProt P61769). Its primary biological role is to stabilize the MHC Class I heterodimer and facilitate the transport of the complex to the cell membrane, where it presents intracellular peptides to CD8+ cytotoxic T cells (PubMed: 28222159). In the context of allogeneic cell therapy, the B2M gene in donor T cells is a critical target for genetic ablation to create "off-the-shelf" Chimeric Antigen Receptor (CAR) T-cell products. By knocking out the B2M gene using technologies like CRISPR/Cas9 or TALENs, researchers can eliminate surface HLA Class I expression, thereby shielding the donor cells from recognition and rejection by the recipient's immune system, known as Host-versus-Graft (HvG) rejection (PubMed: 30718814). This modification is essential for the development of universal donor cells that can be administered to multiple patients without HLA matching. However, the loss of MHC Class I can trigger Natural Killer (NK) cell-mediated lysis due to the "missing self" recognition mechanism, which remains a significant therapeutic challenge in the persistence of these engineered cells (Nature Communications: 32518241).

Other names

B2MBeta-2-microglobulinCD242MHC Class I light chain

Targeted gene knockout to prevent HLA Class I surface expression and evade host immune rejection.