MHC class I polypeptide–related sequence A (MICA)

MHC class I polypeptide–related sequence A (MICA) is a highly polymorphic, stress-inducible cell surface glycoprotein encoded by the *MICA* gene on chromosome 6, within the MHC locus[1][2][5]. Although structurally similar to classical MHC class I molecules, MICA does not associate with β2-microglobulin or present peptides; instead, it serves as a ligand for the activating immunoreceptor NKG2D, which is present on the surface of natural killer (NK) cells, γδ T cells, and subsets of CD8^+^ T cells[1][2][3]. MICA is normally expressed at low levels but is upregulated in response to cellular stress, infection, transformation, or tissue damage, and is recognized as a “danger” signal by cytotoxic lymphocytes[2][4]. In cancer, MICA is broadly upregulated but often found intracellularly or shed as a soluble protein, which can impair immune surveillance[4]. MICA therefore plays important roles in the immune surveillance of tumors and infected cells, in graft rejection, and as a potential biomarker for disease monitoring and therapy response[2][4].

Other names

MHC class I chain-related protein Amajor histocompatibility complex class I chain-related protein AMICA

MICA acts as ligand; drugs might block MICA-NKG2D interaction or modulate its cell-surface presentation, but specific mechanisms largely under clinical investigation rather than established pharmacologies