RT Journal Article
T1 A GPI anchor explains the unique biological features of the common NKG2D-ligand allele MICA*008
A1 Ashiru, Omodele
A1 López-Cobo, Sheila
A1 Fernández Messina, Lola María
A1 Lola Fernández-Messina, 
A1 Pontes-Quero, Samuel
A1 Pandolfi, Rachele
A1 Reyburn, Hugh 
A1 Valés-Gómez, Mar
AB The human MICA (MHC I-related chain A) gene, encoding a ligand for the NKG2D (NKG2-D type II integral membrane protein) receptor, is highly polymorphic. A group of MICA alleles, named MICA 5.1 (prototype, MICA*008), produce a truncated protein due to a nucleotide insertion in the transmembrane domain. These alleles are very frequent in all of the human populations studied and they have different biological properties, compared with full-length alleles, e.g. recruitment into exosomes, which makes them very potent for down-modulating the NKG2D receptor in effector immune cells. Moreover, MICA*008 is not affected by viral immune evasion mechanisms that target other MICA alleles. In the present study, we demonstrate that MICA*008 acquires a GPI (glycosylphosphatidylinositol) anchor and that this modification is responsible for many of the distinct biological features of the truncated MICA alleles, including recruitment of the protein to exosomes. MICA*008 processing is also unusual as it is observed in the endoplasmic reticulum as a Triton™ X-114 soluble protein, partially undergoing GPI modification while the rest is exocytosed, suggesting a new model for MICA*008 release. This is the first report of a GPI-anchored MICA allele. The finding that this modification occurs in both families of human NKG2D ligands, as well as in the murine system, suggests positive pressure to maintain this biochemical feature.
SN 0264-6021
YR 2013
FD 2013
LK https://hdl.handle.net/20.500.14352/97172
UL https://hdl.handle.net/20.500.14352/97172
LA eng
NO Ashiru, Omodele, et al. «A GPI Anchor Explains the Unique Biological Features of the Common NKG2D-Ligand Allele MICA*008». Biochemical Journal, vol. 454, n.o 2, septiembre de 2013, pp. 295-302. https://doi.org/10.1042/BJ20130194.
NO FUNDINGThis work was supported by the Medical Research Council [New Investigator grant number G0601165 (to M.V.-G.)], the Royal Society [grant number IJP2007/R3] and Fondo de Investigación Sanitaria [grant numbers PS09/00181, PI08/1701 and PI11/00298]. O.A. was partially supported by The Newton Trust and the Leukaemia Research Fund [grant number 05060 (to H.T.R. and M.V.-G.)]; S.L.-C. was partially supported by CSIC (Consejo Superior de Investigaciones Científicas) [grant number 201020E086 (to M.V.-G.)]; L.F.-M. was partially supported by CSIC [grant 201020I044 (to M.V.-G.)] and the Comunidad de Madrid [grant number S2010/BMD-2326 IMMUNOTHERCAN (to M.V.-G.)]; R.P. was an exchange student of the Leonardo da Vinci program; and S.P.-Q. was a recipient of a CSIC fellowship of Introduction to Research.
NO Medical Research Council (UK)
NO Royal Society  (UK)
NO Consejo Superior de Investigaciones Científicas
DS Docta Complutense
RD 2 may 2025