Le Gall

Sylvie Le Gall, Ph.D., Assistant Professor of Medicine

Lab Info:

Principal Investigator: Sylvie Le Gall, Ph.D., Assistant Professor of Medicine

Lab Staff: 2 postdoctoral fellows, 2 PhD student, 2 undergraduate student, 2 research technicians. Currently accepting applications fror Ph.D. training or a postdoctoral fellowship. Contact Dr. Le Gall for more information.

Office/Location: 400TS 862

Phone: (857) 268-7010

Email: sylvie_legall@hms.harvard.edu

Category: Group Leaders, Members

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, MTb infections or vaccination. 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, 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.


Applicants interested in pursuing an undergraduate thesis, a Master, Ph.D. or postdoctoral training should submit a letter of application and CV in PDF format to the PI by email.


Dr Le Gall is a faculty of the Harvard Virology Ph.D. Program.


Present Areas of Investigation

  • Mechanisms of antigen processing and presentation in primary cells relevant to HIV 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 peptidome in HIV or Mtb infection
  • Proteomics identification of pathogen-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

Important Accomplishments

  • 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

Publications of Interest

An updated list of relevant publications can be found here



Kulkarni S, Ramsuran V, Rucevic M, Singh S, Lied A, Kulkarni V, O’hUigin C, Le Gall S, Carrington M. Posttranscriptional Regulation of HLA-A Protein Expression by alternative Polyadenylation Signals Involving the RNA-Bisnding Protein Syncrip. J Immunol. 2017 Dec 1;199(11):3892-99.



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



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.



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.



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. Immunology. 2014 2014 Nov 1;193(9):4322-34.



Kourjian, G, Yang X, Mondesire-Crump I, Shimada M, Gourdain P, Le Gall S. Sequence-Specific Alterations of Epitope Production by HIV Protease Inhibitors  J. Immunology. 2014 Mar 10.



Gourdain P, Boucau J, Kourjian G, Lai NY, Duong E, Le Gall S. A real-time killing assay to follow viral epitope presentation to CD8 T cells.  J Immunol Methods. 2013 Dec 15;398-399:60-7.



Zhang S.C., Martin E., Shimada M., Godfrey S.B., Fricke J., Locastro S., Lai N.Y., Paul Liebesny P., Carlson J.M., Brumme C.J., Ogbechie T.A., Chen H.C., Bruce D. Walker B.D., Brumme Z.L., Kavanagh D.G., Le Gall S. Aminopeptidase Substrate Preference Impacts HIV Epitope Presentation and Predicts Immune Escape Patterns in HIV-infected Persons.  J. Immunol 2012 Jun 15;188(12):5924-34


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.



Lazaro E, Godfrey SB, Stamegna P, Ogbechie T, Kerrigan C, Zhang M, Walker BD, Le Gall S. Differential HIV epitope processing in monocytes and CD4 T cells affects cytotoxic T lymphocyte recognition. Infectious Disease 2009 Jul 15;200(2):236-43.



Le Gall S, Stamegna P, Walker BD. Portable flanking sequences modulate CTL epitope processing. J Clin. Invest. 2007 Nov;117(11):3563-75.



Draenert R1, Le Gall S1, Pfafferott K1, Leslie A, Chetty P, Brander C, Holmes C, Chang S-C, Feeney M, Addo M, Ruiz L, Ramduth D, Jeena R, Altfeld M, Thomas S, Tang Y, Verrill C, Dixon C, Prado J, Kiepiela J, Martinez-Picado J, Walker B, Goulder P. Immune selection for altered antigen processing leads to CTL escape in chronic HIV-1 infection.  1. Co-first authors J Exp Med 2004 199(5):905-15. 1



Laboratory Members

Julie Boucau

Julie Boucau, Senior Research Scientist

Vaughn Youngblood, Research Technician


Meera Shankar, Research Technician