Mutational analysis of immunoreceptor tyrosine-based inhibition motifs of the Ig-like transcript 2 (CD85j) leukocyte receptor

The Journal of Immunology : Official Journal of the American Association of Immunologists
Teresa BellónMiguel López-Botet

Abstract

The inhibitory receptor Ig-like transcript (ILT)2 (leukocyte Ig-like receptor or CD85j) is a type I transmembrane protein expressed by different leukocyte lineages. The extracellular region of ILT2 binds HLA class I molecules, and its cytoplasmic domain displays four immunoreceptor tyrosine-based inhibition motifs. Upon tyrosine phosphorylation ILT2 recruits the Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) that is involved in negative signaling. To address the structural basis of ILT2-mediated inhibitory signaling, deletion and single tyrosine mutants were generated and transfected in the COS-7 and rat basophilic leukemia cell lines; their abilities to bind SHP-1 and to inhibit FcepsilonR-induced serotonin release in rat basophilic leukemia cells were studied. Both biochemical and functional analyses revealed tyrosines 644 (SIYATL) and 614 (VTYAQL) as the SHP-1 docking sites required for ILT2 inhibitory function. Substitution of tyrosine 562 (VTYAEV) did not alter receptor function. By contrast, mutation of tyrosine 533 (NLYAAV) interfered with ILT2 tyrosine phosphorylation and the subsequent SHP-1 recruitment, thus supporting a regulatory role for this motif.

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Citations

Nov 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Helena AguilarMiguel López-Botet
Jan 5, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Damiana Alvarez-ErricoMiguel López-Botet
Sep 28, 2007·Journal of Leukocyte Biology·Claudia S WagnerBenedict J Chambers
Nov 9, 2019·Cellular & Molecular Immunology·Zunling LiCheng Cheng Zhang
Oct 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sheryl E Kirwan, Deborah N Burshtyn
Nov 19, 2004·European Journal of Immunology·Damiana Alvarez-ErricoMiguel López-Botet
Mar 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Changlin LiJack L Strominger
Jan 12, 2012·Viral Immunology·José PeñaUNKNOWN Dc2-Manon07 Vaccine Research Group
Nov 11, 2017·Oncoimmunology·Mónica Villa-ÁlvarezSegundo Gonzalez
Jun 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mathias FaureEric O Long
Aug 10, 2006·European Journal of Immunology·Siyuan LiangAnatolij Horuzsko
May 15, 2007·Immunological Reviews·Jakub Abramson, Israel Pecht
Mar 13, 2018·The Journal of Clinical Investigation·Kang YuDeborah N Burshtyn
Jan 9, 2019·Frontiers in Immunology·Mónica Villa-ÁlvarezSegundo Gonzalez
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tsufit Gonen-GrossOfer Mandelboim
Jan 8, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Massimo MaffeiErmanno Ciccone
Mar 5, 2010·European Journal of Immunology·Adriana Monsiváis-UrendaRoberto González-Amaro
Apr 16, 2020·Cancers·Lizeth G Meza GuzmanSandra E Nicholson
May 28, 2021·EMBO Reports·Shannon M Kelley, Kodi S Ravichandran

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