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Cross‐linking of MHC class I molecules on human NK cells inhibits NK cell function, segregates MHC I from the NK cell synapse, and induces intracellular phosphotyrosines
Author(s) -
Rubio Gonzalo,
Férez Xavier,
SánchezCampillo María,
Gálvez Jesús,
Martí Salvador,
Verdú Rocío,
HernándezCaselles Trinidad,
GarcíaPeñarrubia Pilar
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1103597
Subject(s) - biology , mhc class i , major histocompatibility complex , microbiology and biotechnology , immunological synapse , mhc restriction , natural killer cell , transporter associated with antigen processing , cytotoxic t cell , cd1 , lipid raft , t cell , antigen presenting cell , immune system , signal transduction , immunology , t cell receptor , biochemistry , in vitro
Engagement of major histocompatibility complex (MHC) class I molecules on immune cells, where they are usually highly expressed, induces signal transduction events of unclear significance. We show here that antibody‐mediated cross‐linking of MHC‐I molecules on human natural killer (NK) cells inhibits their cytotoxic activity against tumor target cells. Inhibition by anti‐MHC class I monoclonal antibody exhibits molecular specificity and is an isotype and Fc‐independent process. Physical hindrance of specific molecular recognition, induction of apoptosis, or reciprocal NK cell killing, which could be induced by cross‐linking of MHC I molecules, has also been ruled out as putative mechanisms of inhibition. Confocal microscopy analysis revealed that MHC class I molecules on the surface of NK cells colocalize constitutively with GM1, a marker of lipid rafts. Cross‐linking of MHC class I resulted in the asymmetric redistribution of GM1‐enriched raft domains, which are concentrated to the immunological synapse, and MHC I molecules, which segregate to the opposite pole. Also, the cross‐linking of MHC I on NK cells induced intracellular tyrosine phosphorylations. These results suggest that MHC I molecules on NK cells could transmit inhibitory signals upon engagement with putative ligands expressed on the surface of those cells that need to be protected from natural cytotoxicity.