HLA-DR alpha 2 mediates negative signalling via binding to Tirc7 leading to anti-inflammatory and apoptotic effects in lymphocytes in vitro and in vivo.
Classically, HLA-DR expressed on antigen presenting cells (APC) initiates lymphocyte activation via presentation of peptides to TCR bearing CD4+ T-Cells. Here we demonstrate that HLA-DR alpha 2 domain (sHLA-DRalpha2) also induces negative signals by engaging TIRC7 on lymphocytes. This interaction in...
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2008
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oai:doaj.org-article:f93ba63cc3d54d8b9ebdecf43a0818942021-11-25T06:13:26ZHLA-DR alpha 2 mediates negative signalling via binding to Tirc7 leading to anti-inflammatory and apoptotic effects in lymphocytes in vitro and in vivo.1932-620310.1371/journal.pone.0001576https://doaj.org/article/f93ba63cc3d54d8b9ebdecf43a0818942008-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18270567/?tool=EBIhttps://doaj.org/toc/1932-6203Classically, HLA-DR expressed on antigen presenting cells (APC) initiates lymphocyte activation via presentation of peptides to TCR bearing CD4+ T-Cells. Here we demonstrate that HLA-DR alpha 2 domain (sHLA-DRalpha2) also induces negative signals by engaging TIRC7 on lymphocytes. This interaction inhibits proliferation and induces apoptosis in CD4+ and CD8+ T-cells via activation of the intrinsic pathway. Proliferation inhibition is associated with SHP-1 recruitment by TIRC7, decreased phosphorylation of STAT4, TCR-zeta chain & ZAP70, and inhibition of IFN-gamma and FasL expression. HLA-DRalpha2 and TIRC7 co-localize at the APC-T cell interaction site. Triggering HLA-DR - TIRC7 pathway demonstrates that sHLA-DRalpha2 treatment inhibits proinflammatory-inflammatory cytokine expression in APC & T cells after lipopolysaccaride (LPS) stimulation in vitro and induces apoptosis in vivo. These results suggest a novel antiproliferative role for HLA-DR mediated via TIRC7, revise the notion of an exclusive stimulatory interaction of HLA-DR with CD4+ T cells and highlights a novel physiologically relevant regulatory pathway.Grit-Carsta BulwinStephanie WälterMirko SchlawinskyThomas HeinemannAnke SchulzeWolfgang HöhneGerd KrauseWiltrud Kalka-MollPatricia FraserHans-Dieter VolkJürgen LöhlerEdgar L MilfordNalân UtkuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 2, p e1576 (2008) |
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EN |
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Medicine R Science Q |
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Medicine R Science Q Grit-Carsta Bulwin Stephanie Wälter Mirko Schlawinsky Thomas Heinemann Anke Schulze Wolfgang Höhne Gerd Krause Wiltrud Kalka-Moll Patricia Fraser Hans-Dieter Volk Jürgen Löhler Edgar L Milford Nalân Utku HLA-DR alpha 2 mediates negative signalling via binding to Tirc7 leading to anti-inflammatory and apoptotic effects in lymphocytes in vitro and in vivo. |
| description |
Classically, HLA-DR expressed on antigen presenting cells (APC) initiates lymphocyte activation via presentation of peptides to TCR bearing CD4+ T-Cells. Here we demonstrate that HLA-DR alpha 2 domain (sHLA-DRalpha2) also induces negative signals by engaging TIRC7 on lymphocytes. This interaction inhibits proliferation and induces apoptosis in CD4+ and CD8+ T-cells via activation of the intrinsic pathway. Proliferation inhibition is associated with SHP-1 recruitment by TIRC7, decreased phosphorylation of STAT4, TCR-zeta chain & ZAP70, and inhibition of IFN-gamma and FasL expression. HLA-DRalpha2 and TIRC7 co-localize at the APC-T cell interaction site. Triggering HLA-DR - TIRC7 pathway demonstrates that sHLA-DRalpha2 treatment inhibits proinflammatory-inflammatory cytokine expression in APC & T cells after lipopolysaccaride (LPS) stimulation in vitro and induces apoptosis in vivo. These results suggest a novel antiproliferative role for HLA-DR mediated via TIRC7, revise the notion of an exclusive stimulatory interaction of HLA-DR with CD4+ T cells and highlights a novel physiologically relevant regulatory pathway. |
| format |
article |
| author |
Grit-Carsta Bulwin Stephanie Wälter Mirko Schlawinsky Thomas Heinemann Anke Schulze Wolfgang Höhne Gerd Krause Wiltrud Kalka-Moll Patricia Fraser Hans-Dieter Volk Jürgen Löhler Edgar L Milford Nalân Utku |
| author_facet |
Grit-Carsta Bulwin Stephanie Wälter Mirko Schlawinsky Thomas Heinemann Anke Schulze Wolfgang Höhne Gerd Krause Wiltrud Kalka-Moll Patricia Fraser Hans-Dieter Volk Jürgen Löhler Edgar L Milford Nalân Utku |
| author_sort |
Grit-Carsta Bulwin |
| title |
HLA-DR alpha 2 mediates negative signalling via binding to Tirc7 leading to anti-inflammatory and apoptotic effects in lymphocytes in vitro and in vivo. |
| title_short |
HLA-DR alpha 2 mediates negative signalling via binding to Tirc7 leading to anti-inflammatory and apoptotic effects in lymphocytes in vitro and in vivo. |
| title_full |
HLA-DR alpha 2 mediates negative signalling via binding to Tirc7 leading to anti-inflammatory and apoptotic effects in lymphocytes in vitro and in vivo. |
| title_fullStr |
HLA-DR alpha 2 mediates negative signalling via binding to Tirc7 leading to anti-inflammatory and apoptotic effects in lymphocytes in vitro and in vivo. |
| title_full_unstemmed |
HLA-DR alpha 2 mediates negative signalling via binding to Tirc7 leading to anti-inflammatory and apoptotic effects in lymphocytes in vitro and in vivo. |
| title_sort |
hla-dr alpha 2 mediates negative signalling via binding to tirc7 leading to anti-inflammatory and apoptotic effects in lymphocytes in vitro and in vivo. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2008 |
| url |
https://doaj.org/article/f93ba63cc3d54d8b9ebdecf43a081894 |
| work_keys_str_mv |
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