CTL Clonotypes with Higher TCR Affinity Have Better Ability to Reduce the HIV Latent Reservoir
Abstract
The success of the shock and kill strategy for the HIV cure depends both on the reactivation of the latent reservoir and on the ability of the immune system to eliminate infected cells. As latency reversal alone has not shown any impact in the size of the latent reservoir, ensuring that effector CTLs are able to recognize and kill HIV-infected cells could contribute to reservoir reduction. In this study, we investigated which functional aspects of human CTLs are associated with a better capacity to kill HIV-infected CD4+ T cells. We isolated Gag- and Nef-specific CTL clones with different TCR sequences from the PBMC of donors in acute and chronic infection. High-affinity clonotypes that showed IFN-γ production preserved even when the CD8 coreceptor was blocked, and clones with high Ag sensitivity exhibited higher efficiency at reducing the latent reservoir. Although intrinsic cytotoxic capacity did not differ according to TCR affinity, clonotypes with high TCR affinity showed a better ability to kill HIV-infected CD4+ T cells obtained from in vivo–infected PBMC and subjected to viral reactivation. Strategies aiming to specifically boost and maintain long-living memory CTLs with high TCR affinity in vivo prior to latency-reversing treatment might improve the efficacy of the shock and kill approach to reduce the latent reservoir.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 01, 2020
- Source ID
- 10.4049/jimmunol.1900811
Entities
People
- Aaron Sy
- Alexander Haregot
- Ayanna Garland
- Hiroshi Takata
- Jean-Pierre Routy
- Julie Mitchell
- Lydie Trautmann
- Nelson Michael
- Noemia S Lima
- Pearline Cartwright
- R. Brad Jones
- Stephen Blackmore
- Szu-Han Huang
- Victor Appay
Organizations
- George Washington University
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Kumamoto University
- McGill University
- National Institute of Allergy and Infectious Diseases
- Oregon Health & Science University
- Sorbonne University
- United States Army
- Walter Reed Army Institute of Research
- Weill Cornell Medicine