Major histocompatibility complex class I chain-related protein A (MICA)

Major histocompatibility complex class I chain-related protein A (MICA) is a highly polymorphic, stress-inducible cell surface glycoprotein encoded within the MHC locus on chromosome 6. MICA does not present peptide antigens and does not associate with β2-microglobulin, distinguishing it from classical MHC class I proteins. Instead, MICA functions as a ligand for the NKG2D receptor, which is expressed on natural killer (NK) cells, γδ T cells, and CD8+ αβ T cells, activating immune responses against stressed, transformed (e.g., tumor), or infected cells. Unlike classical MHC class I molecules, MICA’s expression is absent from most healthy tissues, but is induced under stress, including cellular transformation and infection. MICA is broadly expressed by a variety of tumor types and certain normal epithelia, primarily within intracellular compartments with only a minor fraction at the cell surface. High genetic polymorphism contributes to complex disease association profiles. Shedding of MICA from the cell surface is linked to tumor immune escape. MICA is a promising immunotherapy target and disease biomarker in several cancers and inflammatory disorders, but clinical therapeutic targeting remains investigational due to complex safety challenges.

Other names

MICAMIC-AMHC class I polypeptide-related sequence APERB11.1

Antibody-based immunotherapy (experimental): antibodies target MICA, aiming to increase immune-mediated elimination of tumor cells by enhancing NKG2D-based recognition. Indirect modulation through immune activation: drugs or strategies that enhance MICA expression may promote anti-tumor immune responses.