Virology Faculty Member - Sylvie Le Gall

Sylvie Le Gall

Assistant Professor of Medicine
Director of the Outreach, Education and Training Program

Ragon Institute of MGH, MIT, and Harvard
Harvard Medical School/ Massachusetts General Hospital
400 Technology Square
Cambridge, MA 02139
Tel: 857-268-7010
Fax: 857-268-7142
Email: sylvie_legall@hms.harvard.edu
Visit my lab page here.

T cell immune recognition and clearance of pathogen-infected cells relies on the presentation of pathogen-derived peptides by MHC molecules. These peptides come from the degradation of pathogen-derived antigens by the antigen processing machinery of cellular compartments in which the pathogen enters and replicates. In chronic infections such as HIV or MTb the degradation processes and nature of peptides presentable by cells during infection or latency reversal are neither well defined nor predictable despite their critical role for immune recognition. The Le Gall laboratory studies the mechanisms of protein degradation, epitope processing and presentation to immune cells in the context of HIV, CMV, MTb infections or vaccination using adenovirus- or CMV-based vectors. Using a combination of biochemical, mass spectrometry approaches and computational analyses we define the proteome and peptidome of infected cells, explore the links between degradation patterns of antigens and immunogenicity in natural infection, define sequence signatures associated with peptide processing efficiency. Our goal is to identify and eventually predict pathogen-derived targets and decoys processed and displayed by cells during infection that will inform vaccine immunogen design and also identify novel mechanisms of immune escape.

Our laboratory uses a large array of techniques, including enzymatic assays, biochemical assays to follow follow intracellular virus trafficking and degradation into peptides identified by mass spectrometry, proteomics and peptidomics ID of primary cells during infection, immunological assays to correlate epitope processing in antigen presenting cells and immune recognition, and computational tools to analyze and predict patterns of antigen degradation relevant to vaccine immunogen design.

Present areas of investigation
· Mechanisms of antigen processing and presentation in primary cells relevant to HIV, CMV or MTb infection or to vaccination
· Antigen processing and presentation in HIV infection, latency and latency reversal
· HIV degradation patterns and immunogenicity in HIV spontaneous control and progression
· The conventional and unconventional MHC immunopeptidome in HIV or Mtb infection
· Proteomics identification of virus-derived translation products and degradation peptides during HIV replication
· Impact of vaccine viral vectors and adjuvants on antigen processing and presentation in dendritic cells
· Manipulating the antigen processing machinery to predictably modulate peptide presentation

Previous published findings
· Identification of motifs within and outside epitopes defining and predicting HIV escape mutations at the population level
· Identification of portable flanking sequences to modulate epitope processing and presentation applicable to immunogen design
· Identification of canonical and non-canonical HIV peptides displayed by HIV-infected CD4 T cells defining new immune responses in HIV-persons
· Variable processing of antigens across HIV-infectable cell subsets affecting immune recognition
· Link between antigen processing, presentation or cross-presentation and immunodominance
· Identification of drugs modulating antigen processing and presentation in a sequence-specific manner

Last Update: 9/6/2017

Publications

For a complete listing of publications click here.

Rucevic M, Kourjian G, Boucau J, Blatnik R, Garcia Bertran W, Berberich MJ, Walker BD, Riemer AB, Le Gall S. MHC-bound HIV Peptides Identified from Various Cell Types Reveal Common Nested Peptides and Novel T Cell Responses. J Virol. 2016 Sep 12;90(19):8605-20
https://www.ncbi.nlm.nih.gov/ pubmed/27440904

Kourjian G, Rucevic M, Berberich MJ, Dinter J, Wambua D, Boucau J, Le Gall S. HIV Protease Inhibitor-Induced Cathepsin Modulation Alters Antigen Processing and Cross-Presentation. J Immunol. 2016 May 1;196(9):3595-607. https://www.ncbi.nlm.nih.gov/ pubmed/27009491

Dinter J, Duong E, Lai NY, Berberich MJ, Kourjian G, Bracho-Sanchez E, Chu D, Su H, Zhang SC, Le Gall S. Variable Processing and Cross-presentation of HIV by Dendritic Cells and Macrophages Shapes CTL Immunodominance and Immune Escape. PLoS Pathog. 2015 Mar 17;11(3):e1004725.
https://www.ncbi.nlm.nih.gov/ pubmed/25781895

Dinter J, Gourdain P, Lai NY, Duong E, Bracho-Sanchez E, Rucevic M, Liebesny PH, Xu Y, Shimada M, Ghebremichael M, Kavanagh DG, Le Gall S. Different Antigen-Processing Activities in Dendritic Cells, Macrophages, and Monocytes Lead to Uneven Production of HIV Epitopes and Affect CTL Recognition.
J. Immunology. 2014 2014 Nov 1;193(9):4322-34.
https://www.ncbi.nlm.nih.gov/ pubmed/25230751

Lazaro E., Kadie C., Stamegna P., Zhang S.C., Gourdain P., Lai N.Y., Zhang M., Martinez S.M., Heckerman D., Le Gall S. Variable cytosolic oligopeptide stability plays a critical role in HIV epitope presentation and immune escape. J. Clin. Invest. 2011 Jun: 121(6):2480-92.
https://www.ncbi.nlm.nih.gov/ pubmed/21555856

Le Gall S, Stamegna P, Walker BD. Portable flanking sequences modulate CTL epitope processing.
J Clin. Invest. 2007 Nov;117(11):3563-75.
https://www.ncbi.nlm.nih.gov/ pubmed/17975674