Novel, in-natural-infection subdominant HIV-1 CD8 + T-cell epitopes revealed in human recipients of conserved-region T-cell vaccines
Borthwick, Nicola (The Jenner Institute, University of Oxford)
Lin, Zhansong (Kumamoto University, Japan)
Akahoshi, Tomohiro (Kumamoto University, Japan)
Llano Montero, Anuska (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Silva-Arrieta, Sandra (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Ahmed, Tina (University of Oxford)
Dorrell, Lucy (University of Oxford)
Brander, Christian (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Murakoshi, Hayato (Kumamoto University, Japan)
Takiguchi, Masafumi (Kumamoto University, Japan)
Hanke, Tomáš (University of Oxford)

Fecha:	2017
Resumen:	Fine definition of targeted CD8 + T-cell epitopes and their human leucocyte antigen (HLA) class I restriction informs iterative improvements of HIV-1 T-cell vaccine designs and may predict early vaccine success or failure. Here, lymphocytes from volunteers, who had received candidate HIVconsv vaccines expressing conserved sub-protein regions of HIV-1, were used to define the optimum-length target epitopes and their HLA restriction. In HIV-1-positive patients, CD8 + T-cell responses predominantly recognize immunodominant, but hypervariable and therefore less protective epitopes. The less variable, more protective epitopes in conserved regions are typically subdominant. Therefore, induction of strong responses to conserved regions by vaccination provides an opportunity to discover novel important epitopes. Cryopreserved lymphocytes from vaccine recipients were expanded by stimulation with 15-mer responder peptides for 10 days to establish short term-cell-line (STCL) effector cells. These were subjected to intracellular cytokine staining using serially truncated peptides and peptide-pulsed 721. 221 cells expressing individual HLA class I alleles to define minimal epitope length and HLA restriction by stimulation of IFN-γ and TNF-α production and surface expression of CD107a. Using lymphocyte samples of 12 vaccine recipients, we defined 14 previously unreported optimal CD8 + T-cell HIV-1 epitopes and their four-digit HLA allele restriction (6 HLA-A, 7 HLA-B and 1 HLA-C alleles). Further 13 novel targets with incomplete information were revealed. The high rate of discovery of novel CD8 + T-cell effector epitopes warrants further epitope mining in recipients of the conserved-region vaccines in other populations and informs development of HIV-1/AIDS vaccines.
Ayudas:	European Commission. Horizon 2020 681137
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	PloS one, Vol. 12 (april 2017) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0176418
PMID: 28448594

19 p, 1.4 MB

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