A post-doctoral position is available to study the mechanisms involved in the persistence of highly efficient CD4+ T cell responses in HIV elite controllers. The successful applicant will join the team of Lisa Chakrabarti at the Pasteur Institute in Paris. The position is funded for 3 years by the ANRS.
The rare patients who spontaneously control HIV replication, called HIV elite controllers, develop particularly efficient antiviral T cell responses. Their CD4+ T cells detect HIV antigens with high sensitivity, resulting in sustained effector functions even in the presence of low viremia. We found that controller CD4+ T cells preferentially express shared T cell receptors (TCRs) with a high affinity for HIV Gag antigens, explaining their capacity to detect trace amounts of virus and to trigger potent antiviral responses. Given that high affinity CD4+ T cells are the first to become activated upon encountering HIV antigens, they are at a higher risk of becoming infected. We aim to understand how these cells escape HIV infection and depletion in controller patients. We obtained recent evidence that Gag-specific CD4+ T cells of controllers are less susceptible to HIV entry than those of treated patients, and propose to dissect the mechanism of this resistance.
The postdoctoral fellow will explore the role of the major HIV coreceptor, CCR5, in limiting the infectability of controller CD4+ T cells. Single cell RNAseq experiments will aim at characterizing the activation and differentiation status of HIV-specific CD4+ T cells, with a focus on the expression of CCR5 and its ligands, the b-chemokines. The impact of TCR affinity on b-chemokine production will be evaluated in TCR transfer experiments, to test the notion that strong TCR signaling could increase b-chemokine production, leading to CCR5 downregulation. The postdoctoral fellow will also benefit from an ongoing collaboration with investigators of the HIV controller cohort ANRS CO21 CODEX and computational genomics specialists, to test candidate genes that may be involved in CCR5 regulation. This project should establish the role of CCR5 in naturally controlled HIV infection, and support the rationale for improving therapeutic strategies that aim at CCR5 inhibition.
We are looking for a skilled and highly motivated candidate with:
Expertise in cell sorting will be an asset. Good communication skills in spoken and written English are essential.