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Project #7608
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#7608 : Single cell analysis of HIV-specific CD4+ T cell differentiation
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Name of Applicant : Lisa Chakrabarti
Date of application : 14-12-2016
Unit : Viral Pathogenesis
Location : 22-1-07
Phone : 0145688945
@ Mail : chakra@pasteur.fr

Project context and summary :

HIV infects and depletes CD4+ T cells, leading to a progressive loss of adaptive immune responses and ultimately to AIDS. In addition, HIV preferentially targets HIV-specific CD4+ T cells, resulting in an attrition of the very cells that should orchestrate the antiviral immune response. Due to this preferential depletion, HIV-specific CD4+ T cells are few and remain incompletely characterized. The emergence of single cell technologies opens the opportunity for an in depth analysis of the rare specific CD4+ T cells that persist in the circulation of chronically infected patients. We have sorted single CD4+ T cells specific for the most immunodominant epitope in HIV-1 capsid, using an optimized MHC class II tetramer labeling protocol. We now propose to analyze these single cells by multiplexed real time PCR in a microfluidics device, to define their transcriptional profile. We will analyze the differentiation status of HIV-specific CD4+ T cells in rare patients who naturally control HIV infection and in progressor patients who control HIV replication due to antiretroviral therapy. This project will help define the parameters of an efficient T cell response against HIV, and may provide insights into the type of responses that should be induced by candidate HIV vaccines.


Related team publications :
Benati D.*, Galperin M.*, Lambotte O., Gras S., Lim A., Mukhopadhyay M., Nouël A., Campbell K.A., Lemercier B., Claireaux M., Hendou S., Lechat P., De Truchis P., Boufassa F., Rossjohn J., Delfraissy J.F., Arenzana-Seisdedos F., and Chakrabarti L.A. (2016) Public TCRs confer high-avidity CD4 responses to HIV Controllers. Journal of Clinical Investigation 26:2093-2108 doi: 10.1172/JCI83792
Vingert B.*, Benati D.*, Lambotte O., de Truchis P., Slama L., Jeannin P., Galperin M., Perez-Patrigeon S., Boufassa F., Kwok W. W., Lemaitre F., Delfraissy J. F., Theze J., and Chakrabarti L. A. (2012) HIV Controllers maintain a population of highly efficient Th
Vingert B., Perez-Patrigeon S., Jeannin P., Lambotte O., Boufassa F., Lemaître F., Kwok W.W., Theodorou I., Delfraissy J.F., Thèze J., and Chakrabarti L.A. ; for the ANRS EP36 HIV Controllers Study Group. (2010) HIV Controllers CD4+ T cells respond to minimal amounts of Gag antigen due to high TCR avidity. PLoS Pathogens 6(2): e1000780
Service Delivery
Project Manager : stevenn.volant@pasteur.fr
Project Type : Medium
Status : Awaiting Publication
Global Satisfaction for this application : Excellent (5/5)


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