MHC class I polypeptide-related sequence A and MHC class I polypeptide-related sequence B (MICA and MICB)

MHC class I polypeptide-related sequence A (MICA) and MHC class I polypeptide-related sequence B (MICB) are highly polymorphic, stress-induced cell surface glycoproteins structurally related to classical MHC class I molecules[1][7]. Both are encoded within the MHC locus on chromosome 6 and serve as ligands for the activating receptor NKG2D found on natural killer (NK) cells, γδ T cells, and cytotoxic αβ T cells[1][2][6][7][8]. Unlike classical MHC class I proteins, MICA and MICB do not bind β2-microglobulin nor present peptides; instead, they act as danger signals, becoming upregulated in response to cellular stress (infection, transformation, heat shock, or DNA damage)[1][7][4]. Upon recognition by NKG2D-expressing lymphocytes, they trigger immune-mediated destruction of stressed, damaged, or transformed cells, especially tumor cells[2][3][9]. MICA and MICB are usually not expressed on healthy cells but are upregulated in many tumor types and in certain inflammatory or autoimmune conditions[2][9]. Shedding of soluble MICA/B (sMICA/sMICB) by proteolytic cleavage can enable tumor immune evasion by downregulating NKG2D and suppressing the anti-tumor immune response; high levels of sMICA/B are associated with poor cancer prognosis[6][9]. Genetic variation in MICA/MICB is linked to susceptibility and outcome in various cancers, infections, and autoimmune diseases[3][4][6]. There are currently no approved therapies specifically targeting MICA or MICB, but this axis is under research for cancer immunotherapy and biomarker applications[2][6][9].

Other names

MICA: MIC-A, PERB11.1MICB: MIC-B, PERB11.2

Antibody or small molecule can enhance anti-tumor immune response by blocking MICA/MICB shedding or engaging NKG2D-mediated activation of NK and cytotoxic T cells[2][6][9].