Dissociation of peripheral T cell responses from thymocyte negative selection by weak agonists supports a spare receptor model of T cell activation

Proceedings of the National Academy of Sciences of the United States of America
Lisa K McNeil, Brian D Evavold

Abstract

We have focused on stability of the peptide-MHC complex as a determining factor of ligand potency for thymocytes and peripheral CD4+ T cell responses. MHC variant peptides that have low affinities and fast dissociation rates are different in that they stimulate proliferation and cytolysis of mature T cells (classifying the variant peptides as weak agonists) but do not induce thymocyte negative selection. The MHC variant weak agonists require significant receptor reserve, because decreasing the level of T cell receptor on mature T cells blocks the proliferative response. These results demonstrate that peripheral T cells are more sensitive to MHC variant ligands by virtue of increased T cell receptor expression; in addition, the data support a T cell model of the spare receptor theory.

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Citations

Nov 12, 2009·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Joseph J SabatinoBrian D Evavold
Jan 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yifan ZhanAndrew M Lew
Jul 13, 2013·FEBS Open Bio·Laurent JacquinJean Ruf
Jun 12, 2012·Molecular Immunology·Jun HuangCheng Zhu
Mar 26, 2005·Immunological Reviews·Teresa P DiLorenzo, David V Serreze
Jul 13, 2007·Immunological Reviews·Peter ReichardtMatthias Gunzer
Jul 31, 2013·Journal of Autoimmunity·Lindsay J Edwards, Brian D Evavold
Sep 10, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lori BlanchfieldBrian D Evavold
Apr 19, 2005·The Journal of Membrane Biology·Y MarunakaH Miyazaki
May 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kyoo Y LeeRho H Seong
Jan 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lisa K McNeil, Brian D Evavold
Jul 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniel S JonesBrian D Evavold
Sep 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Caroline-Morgane Choisy-RossiDavid V Serreze
May 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heather A Wasserman, Brian D Evavold
Dec 17, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christina K BaumgartnerLaurent P Malherbe
Dec 1, 2019·International Journal of Molecular Sciences·Emmanuel FenouilletJean Ruf
Feb 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·David V SerrezeMichele P Marron
Jul 25, 2021·International Journal of Molecular Sciences·Régis GuieuJean Ruf

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