scholarly journals Presentation of Acquired Peptide-MHC Class II Ligands by CD4+ Regulatory T Cells or Helper Cells Differentially Regulates Antigen-Specific CD4+ T Cell Response

2011 ◽  
Vol 186 (4) ◽  
pp. 2148-2155 ◽  
Author(s):  
Gang Zhou ◽  
Zhi-Chun Ding ◽  
Jie Fu ◽  
Hyam I. Levitsky
Author(s):  
Sophia Schulte ◽  
Janna Heide ◽  
Christin Ackermann ◽  
Sven Peine ◽  
Michael Ramharter ◽  
...  

Abstract Relatively little is known about the ex vivo frequency and phenotype of the P. falciparum-specific CD4+ T cell response in humans. The exported protein 1 (EXP1) is expressed by plasmodia at both, the liver stage and blood stage, of infection making it a potential target for CD4+ and CD8+ effector T cells. Here, a fluorochrome-labelled HLA-DRB1*11:01-restriced MHC class II tetramer derived from the P. falciparum EXP1 (aa62-74) was established for ex vivo tetramer analysis and magnetic bead enrichment in ten patients with acute malaria. EXP1-specific CD4+ T cells were detectable in nine out of ten (90%) malaria patients expressing the HLA-DRB1*11 molecule with an average ex vivo frequency of 0.11% (0-0.22%) of total CD4+ T cells. The phenotype of EXP1-specific CD4+ T cells was further assessed using co-staining with activation (CD38, HLA-DR, CD26), differentiation (CD45RO, CCR7, KLRG1, CD127), senescence (CD57) and co-inhibitory (PD-1, TIGIT, LAG-3, TIM-3) markers as well as the ectonucleotidases CD39 and CD73. EXP1-specific tetramer+ CD4+ T cells had a distinct phenotype compared to bulk CD4+ T cells and displayed a highly activated effector memory phenotype with elevated levels of co-inhibitory receptors and activation markers: EXP1-specific CD4+ T cells universally expressed the co-inhibitory receptors PD-1 and TIGIT as well as the activation marker CD38 and showed elevated frequencies of CD39. These results demonstrate that MHC class II tetramer enrichment is a sensitive approach to investigate ex vivo antigen-specific CD4+ T cells in malaria patients that will aid further analysis of the role of CD4+ T cells during malaria.


2014 ◽  
Vol 73 (Suppl 1) ◽  
pp. A45.3-A46
Author(s):  
H Leiss ◽  
B Schwarzecker ◽  
I Gessl ◽  
B Niederreiter ◽  
JS Smolen ◽  
...  

2012 ◽  
Vol 64 (7) ◽  
pp. 507-523 ◽  
Author(s):  
Kaitlyn Morse ◽  
Junzo Norimine ◽  
Jayne C. Hope ◽  
Wendy C. Brown

2000 ◽  
Vol 165 (3) ◽  
pp. 1285-1293 ◽  
Author(s):  
Jean-Paul Kovalik ◽  
Nagendra Singh ◽  
Sanjeev K. Mendiratta ◽  
W. David Martin ◽  
Leszek Ignatowicz ◽  
...  

2012 ◽  
Vol 80 (9) ◽  
pp. 3279-3288 ◽  
Author(s):  
Harshita Satija Grover ◽  
Nicolas Blanchard ◽  
Federico Gonzalez ◽  
Shiao Chan ◽  
Ellen A. Robey ◽  
...  

ABSTRACTThe apicomplexan parasiteToxoplasma gondiican cause severe disease in immunocompromised individuals. Previous studies in mice have focused largely on CD8+T cells, and the role of CD4 T cells is relatively unexplored. Here, we show that immunization of the C57BL/6 strain of mice, in which the immunodominant CD8 T cell response to the parasite dense-granule protein GRA6 cannot be generated, leads to a prominent CD4 T cell response. To identify the CD4 T cell-stimulating antigens, we generated aT. gondii-specific,lacZ-inducible, CD4 T cell hybridoma and used it as a probe to screen aT. gondiicDNA library. We isolated a cDNA encoding a protein of unknown function that we call CD4Ag28m and identified the minimal peptide, AS15, which was presented by major histocompatibility complex (MHC) class II molecules to the CD4 T cells. Immunization of mice with the AS15 peptide provided significant protection against subsequent parasite challenge, resulting in a lower parasite burden in the brain. Our findings identify the first CD4 T cell-stimulating peptide that can confer protection against toxoplasmosis and provide an important tool for the study of CD4 T cell responses and the design of effective vaccines against the parasite.


2009 ◽  
Vol 69 (10) ◽  
pp. 4335-4345 ◽  
Author(s):  
Violaine François ◽  
Sabrina Ottaviani ◽  
Nicolina Renkvist ◽  
Julie Stockis ◽  
Gerold Schuler ◽  
...  

2014 ◽  
Vol 73 (Suppl 2) ◽  
pp. 861.4-862
Author(s):  
H. Leiss ◽  
B. Schwarzecker ◽  
I. Gessl ◽  
W. Salzberger ◽  
A. Puchner ◽  
...  

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