Immunobiology of the human MHC class I chain-related gene A (MICA): from transplantation immunology to tumor immune escape

ZWIRNER, NORBERTO WALTER; FUERTES, MERCEDES BEATRIZ; GIRART, MARÍA VICTORIA; DOMAICA, CAROLINA INÉS; ROSSI, LUCAS EZEQUIEL

Inmunología

Sociedad Española de Inmunología

Lugar: Madrid; Año: 2006 vol. 25 p. 25 - 38

The MHC class I chain-related gene A (MICA) encodes for a distantly MHC class I-related polymorphic glycoprotein not associated with b2-microglobulin mainly expressed by epithelial and non epithelial tumors, gastrointestinal epithelium, freshly isolated human endothelial cells, keratinocytes and fibroblasts, and in thymic medulla. Expression of MICA also has been observed in activated T cells. MICA is recognized by the C-type lectin NKG2D receptor, which is expressed by NK cells, gd and ab CD8+ T lymphocytes. MICA expression is up-regulated in response to infection and neotransformation, resulting in a cytotoxic response and IFN-g secretion mediated by NKG2D-expressing cells. Also, up-regulated expression of MICA under inflammatory conditions and in autoimmune diseases like rheumatoid arthritis, celiac disease and seborrhoeic dermatitis, might contribute to the immunopathology of these illnesses. Furthermore, anti-MICA alloantibodies have been detected in sera of patients who rejected solid organ transplants, indicating that MICA is a target for an alloimmune response during solid organ transplantation. Since MICA is widely expressed on tumors of different histotypes, some interest has been focused on its capacity to trigger an efficient cytotoxic antitumor immune response and secretion of IFN-g by NKG2D-expressing cells. However, recent evidence has demonstrated that tumors developed escape mechanisms that involve the MICA-NKG2D system like shedding of soluble MICA, tumor-derived TGF-b-induced down-regulation of NKG2D and MICA, and intracellular retention of MICA, which impair the immunosurveillance process. In this review we address these issues in detail and summarize current concepts about the immunobiology of MICA.