Title:MICA Molecules in Disease and Transplantation, a Double-Edged Sword?
Volume: 8
Issue: 4
Author(s): Manuel Muro, Ruth Lopez-Hernandez, Santiago Llorente, Jose Miguel Bolarin, Pedro Martinez, Francisco Boix, Gema Salgado, Alexandre Bosch, Helios Martinez, Jorge Eguia, Jose A. Campillo, Maria R. Moya-Quiles, Alfredo Minguela, Ana M. Garcia-Alonso, Luisa Jimeno and Maria R. Alvarez-Lopez
Affiliation:
Keywords:
MICA, transplant, tumours, polymorphism, natural killer (NK), NKG2D, NKG2DL, HLA, MHC, allele
frequencies, homeostasis
Abstract: Major histocompatibility complex class I chain-related member A (MICA) encodes a stress-induced cellsurface
glycoprotein that is expressed in keratinocytes, fibroblasts and gastrointestinal epithelium, among others. MICA is
not associated with β2-microglobulin and does not appear to present peptides. MICA displays a high degree of allele
polymorphism within the non-classical HLA gene loci. The functional significance of these polymorphisms is unknown,
although certain changes in protein amino acid sequence cause an abnormal expression or affinity with NKG2D, its ligand
on the surface of NK, γδ-T and CD8+ lymphocytes, affecting NK-cell activation and T-cell response modulation. Indeed,
many tumoral cells express MICA on their surface, and circulating soluble MICA also triggers NKG2D downregulation
and impairs lymphocyte cytotoxicity in tumoral escape. This demonstrates the therapeutic potential of anti-MICA
antibodies to overcome immune suppression and trigger tumor destruction. MICA also affects organ transplants outcome,
as MICA antigens elicit a very powerful antibody response in recipients of organ allografts. NKG2D ligand induction
might also participate in the amplification loop that leads to tissue damage during acute graft vs. host disease. MICA is
also an important candidate gene for a number of clinically significant diseases, including diabetes, rheumatoid arthritis,
and other autoimmune diseases. This updated version of our previous review highlights the advantages and limitations of
MICA gene studies in several pathologies and transplantation, and critically discusses the most recent and updated
findings in this rapidly evolving field.
