The mouse monoclonal antibody 6D4 recognizes a common extracellular epitope on MICA and MICB glycoproteins, transmembrane ligands of CD314 (NKG2D), and is able to block CD314-mediated activation of NK cells and cytotoxic T cells.
MICA and MICB glycoproteins are members of MHC class I family, closely linked to HLA-B. However, unlike HLA molecules, MICA and MICB are not associated with beta2 microglobulin and are conformationally stable in the absence of conventional MHC class I peptide ligands. Both proteins are stress-induced antigens expressed mainly in gastrointestinal epithelium, where they are recognized by V-delta1 subset of gamma/delta T cells, and also on diverse epithelial tumor cells. Binding of MICA/MICB receptor, the NKG2D, leads to cytolytic response of NK cells, Tc cells, and gamma/delta T cells. Alternative splicing results in multiple isoforms, and some of them have been associated with susceptibility to psoriasis and psoriatic arthritis. Shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma.