MICA immune complex formed with alpha 3 domain-specific antibody activates human NK cells in a Fc-dependent manner

Journal for Immunotherapy of Cancer
Changchun DuZhengmao Ye

Abstract

One of the mechanisms by which tumors evade immune surveillance is through shedding of the major histocompatibility complex (MHC) class I chain-related protein A and B (MICA/B) from their cell surface. MICA/B are ligands for the activating receptor NKG2D on NK and CD8 T cells. This shedding reduces cell surface levels of MICA/B and impairs NKG2D recognition. Shed MICA/B can also mask NKG2D receptor and is thought to induce NKG2D internalization, further compromising immune surveillance by NK cells. We isolated human primary NK cells from normal donors and tested the suppressive activity of soluble recombinant MICA in vitro. Utilizing a panel of novel anti-MICA antibodies, we further examined the stimulatory activities of anti-MICA antibodies that reversed the suppressive effects of soluble MICA. We show that suppressive effects of soluble MICA (sMICA) on NK cell cytolytic activity was not due to the down-regulation of cell surface NKG2D. In the presence of an α3 domain-specific MICA antibody, which did not obstruct NKG2D binding, sMICA-mediated NK cell suppression was completely reversed. Reversal of NK cell inhibition by sMICA was mediated by immune complex formation that agonized NKG2D signaling. Furthermore, this restorative...Continue Reading

References

Mar 22, 2002·Nature Reviews. Immunology·A Cerwenka, L L Lanier
Oct 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Helmut R SalihAlexander Steinle
Mar 21, 2003·Proceedings of the National Academy of Sciences of the United States of America·Roberta CastriconiAlessandro Moretta
May 13, 2003·Nature Immunology·Daniel D BilladeauPaul J Leibson
Oct 3, 2003·Nature Reviews. Immunology·David H Raulet
Dec 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ekaterina S DoubrovinaYatin M Vyas
Aug 12, 2005·International Journal of Cancer. Journal International Du Cancer·Stefan HoldenriederHelmut Rainer Salih
May 16, 2006·Human Immunology·Xiaojiang GaoMary Carrington
Jun 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·Masahisa JinushiGlenn Dranoff
Aug 25, 2006·International Journal of Cancer. Journal International Du Cancer·Angela MärtenJan Schmidt
Jul 7, 2007·Immunology·Anita R Mistry, Chris A O'Callaghan
Jan 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Masahisa JinushiGlenn Dranoff
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sigrid DuboisJürgen R Müller
Aug 5, 2008·Cancer Research·Inja WaldhauerAlexander Steinle
Mar 31, 2018·Science·Lucas Ferrari de AndradeKai W Wucherpfennig

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Citations

Jun 11, 2020·Journal for Immunotherapy of Cancer·Nicolas TorresNorberto Walter Zwirner
Jun 25, 2020·International Journal of Cancer. Journal International Du Cancer·Dhanya RamachandranThilo Dörk
Oct 31, 2020·Signal Transduction and Targeted Therapy·Yuqing CaoFeng Xu
Aug 17, 2021·Frontiers in Immunology·Mercedes Beatriz FuertesNorberto Walter Zwirner

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Methods Mentioned

BETA
FACS
density gradient centrifugation
flow cytometry
ELISA

Software Mentioned

FlowJo
GraphPad Prism

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