The Le Gall laboratory studies the mechanisms of viral protein degradation, epitope processing and presentation to immune cells, with a main focus on HIV infection.

CD8 T cells represent a critical arm of the immune response against HIV-1 infection. They contribute to reducing HIV replication by recognizing HIV epitopes produced via intracellular processing pathways and presented by MHC-I molecules. Thus the degradation of HIV proteins into epitopes, their intracellular association with HLA class I and display at the cell surface represent key steps leading to immune recognition. Any change in the processing of such epitopes may alter the efficiency of CTL responses. Likewise, antigen processing is a key step in the elicitation of vaccine-induced immune responses as one needs to ensure that epitopes included in a vaccine will be properly processed and presented to CTL.

The Le Gall laboratory is interested in the mechanisms of epitope processing in the context of HIV infection in vitro or ex vivo in primary cells from HIV-infected individuals. We aim at defining factors contributing to efficient epitope presentation as well the effect of HIV infection of the antigen processing machinery. Our laboratory uses a large array of techniques, including enzymatic assays to measure peptidase activities, molecular biology techniques to analyze gene and protein expression, biochemical assays to follow in vitro degradation of peptides or proteins followed by HPLC and mass spectrometry analysis of the peptides produced, as well as immunological assays to correlate endogenous epitope processing in antigen presenting cells and CTL killing capacity.

Present Areas of Investigation:
		Evolution of antigen processing activities during the course of HIV infection
		Antigen processing activities in HIV controllers and progressors
		Identification of HIV antigen processing pathways
		Contribution of antigen processing efficiency to the specificity and functionality of CTL responses
		Impact of HIV mutations on epitope processing and CTL escape
Important Accomplishments:
		First demonstration of a link between impaired HIV epitope processing and CTL escape
		Identification of portable flanking sequences that allow to increase or decrease epitope processing and presentation
		Variability of antigen processing activities in cell subsets
Publications of Interest:
	1.	Draenert, R, Le Gall S. et al. Immune selection for altered antigen processing leads to cytotoxic T lymphocyte escape in chronic HIV-1 infection. J Exp Med 199, 905-15 (2004).
	2.	Kavanagh DG, Kaufmann DE, Sunderji S, Frahm N, Le Gall S, Boczkowski D, Rosenberg ES, Stone DR, Johnston MN, Wagner BS, Zaman MT, Brander C, Gilboa E, Walker BD, Bhardwaj N. Expansion of HIV-specific CD4+ and CD8+ T cells by dendritic cells transfected with mRNA encoding cytoplasm- or lysosome-targeted Nef. Blood. 2006 107(5):1963-9. PMC1895708
	3.	Le Gall S, Stamegna P., Walker BD. Portable flanking sequences modulate CTL epitope processing. J Clin Invest. 2007 Nov; 117(11):3563-75.
	4.	Troyer RM, McNevin J, Liu Y, Zhang SC, Krizan RW, Abraha A, Tebit DM, Zhao H, Avila S, Lobritz MA, McElrath MJ, Le Gall S, Mullins JI, Arts EJ. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response. PLoS Pathog. 2009 Apr;5(4):e1000365. PMC2659432
	5.	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. J Infect Dis. 2009 Jul 15;200(2):236-43.
	6.	Le Gall, S. MHC-I-restricted HIV epitope production, immune control and immunogen design. HIV Therapy 2010 Jan: 4 (1):101-117
	7.	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 in press

May 10, 2011
Important step in breakdown of HIV proteins is critical to immune system recognition, destruction of infected cells
Dr. Sylvie Le Gall's laboratory has discovered a key step in the processing of HIV within cells which appears to affect how effectively the immune system's killer T cells can recognize and destroy infected cells. Their report appears in the June Journal of Clinical Investigation.
press release (pdf)