scholarly journals High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Smita K. Nair ◽  
Georgia D. Tomaras ◽  
Ana Paula Sales ◽  
David Boczkowski ◽  
Cliburn Chan ◽  
...  
Immunology ◽  
2011 ◽  
Vol 132 (4) ◽  
pp. 482-491 ◽  
Author(s):  
Mingjun Wang ◽  
Sheila T. Tang ◽  
Anette Stryhn ◽  
Sune Justesen ◽  
Mette V. Larsen ◽  
...  

2014 ◽  
Vol 61 (2) ◽  
pp. 242-251 ◽  
Author(s):  
Patrizia Leone ◽  
Mariangela Di Tacchio ◽  
Simona Berardi ◽  
Teresa Santantonio ◽  
Massimo Fasano ◽  
...  

2016 ◽  
Vol 44 ◽  
pp. 182-189 ◽  
Author(s):  
Iti Saraav ◽  
Kirti Pandey ◽  
Monika Sharma ◽  
Swati Singh ◽  
Prasun Dutta ◽  
...  

2008 ◽  
Vol 205 (3) ◽  
pp. 595-610 ◽  
Author(s):  
Marie-Hélène Fortier ◽  
Étienne Caron ◽  
Marie-Pierre Hardy ◽  
Grégory Voisin ◽  
Sébastien Lemieux ◽  
...  

Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a novel high-throughput mass spectrometry approach that yields an accurate definition of the nature and relative abundance of unlabeled peptides presented by MHC I molecules. We identified 189 and 196 MHC I–associated peptides from normal and neoplastic mouse thymocytes, respectively. By integrating our peptidomic data with global profiling of the transcriptome, we reached two conclusions. The MIP repertoire of primary mouse thymocytes is biased toward peptides derived from highly abundant transcripts and is enriched in peptides derived from cyclins/cyclin-dependent kinases and helicases. Furthermore, we found that ∼25% of MHC I–associated peptides were differentially expressed on normal versus neoplastic thymocytes. Approximately half of those peptides are derived from molecules directly implicated in neoplastic transformation (e.g., components of the PI3K–AKT–mTOR pathway). In most cases, overexpression of MHC I peptides on cancer cells entailed posttranscriptional mechanisms. Our results show that high-throughput analysis and sequencing of MHC I–associated peptides yields unique insights into the genesis of the MIP repertoire in normal and neoplastic cells.


2007 ◽  
Vol 56 (4) ◽  
pp. 466-474 ◽  
Author(s):  
M. G. Chaitra ◽  
M. S. Shaila ◽  
R. Nayak

The PE and PPE proteins of Mycobacterium tuberculosis form a source of antigenic variation among different strains of M. tuberculosis. One of the PE_PGRS proteins, Rv1818c, plays a role in the pathogenesis of mycobacterial infection and specifically influences host-cell responses to tuberculosis infection. Although little is known about these two classes of protein, an immunoinformatics approach has indicated the possibility of their participation in eliciting a major histocompatibility complex (MHC) class I-mediated immune response against tuberculosis, as peptides derived from Rv1818c are predicted to bind to MHC class I molecules with high affinity. In the present work, a DNA vaccine was constructed encoding the full-length Rv1818c protein of M. tuberculosis and its immunogenicity was analysed in BALB/c mice. Immunization with Rv1818c DNA induced a strong CD8+ cytotoxic lymphocyte and Th1-type response, with high levels of gamma interferon (IFN-γ) and low levels of interleukin-4. Two nonameric peptides (Peptide6–14 and Peptide385–393) from Rv1818c were identified by their ability to induce the production of IFN-γ by CD8+ T cells in mice immunized with Rv1818c DNA. An epitope-specific response was demonstrated by the lysis of peptide-pulsed antigen-presenting cells, release of cytotoxic granules and IFN-γ production. These peptides bound with high affinity to MHC H-2Kd and showed low dissociation rates of peptide–MHC complexes. These results could form the basis for testing the identified T-cell epitopes of PE_PGRS proteins in the induction of protective immunity against M. tuberculosis challenge in the mouse model.


2004 ◽  
Vol 172 (4) ◽  
pp. 2126-2136 ◽  
Author(s):  
Fabrice André ◽  
Nathalie Chaput ◽  
Nöel E. C. Schartz ◽  
Caroline Flament ◽  
Nathalie Aubert ◽  
...  

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