title: Dynamic Perturbations of the T-Cell Receptor Repertoire in Chronic HIV Infection and following Antiretroviral Therapy.
abstract: HIV infection profoundly affects many parameters of the immune system and ultimately leads to AIDS, yet which factors are most important for determining resistance, pathology, and response to antiretroviral treatment - and how best to monitor them - remain unclear. We develop a quantitative high-throughput sequencing pipeline to characterize the TCR repertoires of HIV-infected individuals before and after antiretroviral therapy, working from small, unfractionated samples of peripheral blood. This reveals the TCR repertoires of HIV(+) individuals to be highly perturbed, with considerably reduced diversity as a small proportion of sequences are highly overrepresented. HIV also causes specific qualitative changes to the repertoire including an altered distribution of V gene usage, depletion of public TCR sequences, and disruption of TCR networks. Short-term antiretroviral therapy has little impact on most of the global damage to repertoire structure, but is accompanied by rapid changes in the abundance of many individual TCR sequences, decreases in abundance of the most common sequences, and decreases in the majority of HIV-associated CDR3 sequences. Thus, high-throughput repertoire sequencing of small blood samples that are easy to take, store, and process can shed light on various aspects of the T-cell immune compartment and stands to offer insights into patient stratification and immune reconstitution.
authors.affiliation: Division of Infection and Immunity, University College London , London , UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Heather
authors.affiliation: Division of Infection and Immunity, University College London, London, UK; Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX), University College London, London, UK.
authors.forename: Katharine
authors.initials: K
authors.lastname: Best
authors.affiliation: Division of Infection and Immunity, University College London , London , UK.
authors.forename: Theres
authors.initials: T
authors.lastname: Oakes
authors.affiliation: Division of Infection and Immunity, University College London , London , UK.
authors.forename: Eleanor R
authors.initials: ER
authors.lastname: Gray
authors.affiliation: Division of Infection and Immunity, University College London , London , UK.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Roe
authors.affiliation: Division of Infection and Immunity, University College London , London , UK.
authors.forename: Niclas
authors.initials: N
authors.lastname: Thomas
authors.affiliation: Department of Immunology, Weizmann Institute , Rehovot , Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
authors.affiliation: Division of Infection and Immunity, University College London , London , UK.
authors.forename: Mahdad
authors.initials: M
authors.lastname: Noursadeghi
authors.affiliation: Division of Infection and Immunity, University College London , London , UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chain
keywords: AIDS; ART; HIV; T-cell; TCR; repertoire; sequencing