scholarly journals Rapid CD4 + T‐cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9

2014 ◽  
Vol 45 (2) ◽  
pp. 513-524 ◽  
Author(s):  
Shaikh M. Atif ◽  
Seung‐Joo Lee ◽  
Lin‐Xi Li ◽  
Satoshi Uematsu ◽  
Shizuo Akira ◽  
...  
Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 271
Author(s):  
Michele Graciotti ◽  
Fabio Marino ◽  
HuiSong Pak ◽  
Petra Baumgaertner ◽  
Anne-Christine Thierry ◽  
...  

Hypochlorous acid (HOCl)-treated whole tumor cell lysates (Ox-L) have been shown to be more immunogenic when used as an antigen source for therapeutic dendritic cell (DC)-based vaccines, improving downstream immune responses both in vitro and in vivo. However, the mechanisms behind the improved immunogenicity are still elusive. To address this question, we conducted a proteomic and immunopeptidomics analyses to map modifications and alterations introduced by HOCl treatment using a human melanoma cell line as a model system. First, we show that one-hour HOCl incubation readily induces extensive protein oxidation, mitochondrial biogenesis, and increased expression of chaperones and antioxidant proteins, all features indicative of an activation of oxidative stress-response pathways. Characterization of the DC proteome after loading with HOCl treated tumor lysate (Ox-L) showed no significant difference compared to loading with untreated whole tumor lysate (FT-L). On the other hand, detailed immunopeptidomic analyses on monocyte-derived DCs (mo-DCs) revealed a great increase in human leukocyte antigen class II (HLA-II) presentation in mo-DCs loaded with Ox-L compared to the FT-L control. Further, 2026 HLA-II ligands uniquely presented on Ox-L-loaded mo-DCs were identified. In comparison, identities and intensities of HLA class I (HLA-I) ligands were overall comparable. We found that HLA-II ligands uniquely presented by DCs loaded with Ox-L were more solvent exposed in the structures of their source proteins, contrary to what has been hypothesized so far. Analyses from a phase I clinical trial showed that vaccinating patients using autologous Ox-L as an antigen source efficiently induces polyfunctional vaccine-specific CD4+ T cell responses. Hence, these results suggest that the increased immunogenicity of Ox-L is, at least in part, due to qualitative and quantitative changes in the HLA-II ligandome, potentially leading to an increased HLA-II dependent stimulation of the T cell compartment (i.e., CD4+ T cell responses). These results further contribute to the development of more effective and immunogenic DC-based vaccines and to the molecular understanding of the mechanism behind HOCl adjuvant properties.


2017 ◽  
Vol 103 (4) ◽  
pp. 739-748 ◽  
Author(s):  
Erica Bizzell ◽  
Jonathan Kevin Sia ◽  
Melanie Quezada ◽  
Ana Enriquez ◽  
Maria Georgieva ◽  
...  

2019 ◽  
Vol 129 (7) ◽  
pp. 2888-2897 ◽  
Author(s):  
Emma E. Hornick ◽  
Jargalsaikhan Dagvadorj ◽  
Zeb R. Zacharias ◽  
Ann M. Miller ◽  
Ryan A. Langlois ◽  
...  

2018 ◽  
Vol 200 (10) ◽  
pp. 3383-3396 ◽  
Author(s):  
Kuan Y. Wong ◽  
Rebecca Baron ◽  
Therese A. Seldon ◽  
Martina L. Jones ◽  
Alison M. Rice ◽  
...  

2019 ◽  
Vol 202 (4) ◽  
pp. 1045-1056 ◽  
Author(s):  
Danielle D. Kish ◽  
Susie Min ◽  
Nina Dvorina ◽  
William M. Baldwin ◽  
Stephen A. Stohlman ◽  
...  

2006 ◽  
Vol 177 (4) ◽  
pp. 2276-2284 ◽  
Author(s):  
Robert W. Carter ◽  
Clare Thompson ◽  
Delyth M. Reid ◽  
Simon Y. C. Wong ◽  
David F. Tough

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