Format

Send to

Choose Destination
J Immunol. 2014 Dec 1;193(11):5626-36. doi: 10.4049/jimmunol.1401017. Epub 2014 Oct 27.

Epitope specificity delimits the functional capabilities of vaccine-induced CD8 T cell populations.

Author information

1
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
2
Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom;
3
Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom;
4
Mathematics Institute, University of Warwick, Coventry CV4 7AL, United Kingdom;
5
Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales, Australia;
6
INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, F-75013 Paris, France; and Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universités, Université Pierre et Marie Curie (Université Paris 06), CR7, F-75013 Paris, France.
7
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom; ddouek@mail.nih.gov priced6@cardiff.ac.uk.
8
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; ddouek@mail.nih.gov priced6@cardiff.ac.uk.

Abstract

Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2K(d) epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2D(d) epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2D(d) specificity. Higher proportions of central memory-like cells were present after low-dose vaccination and at later time points. However, there were no noteworthy phenotypic differences between epitope-specific CD8 T cell populations across vaccine doses or time points. Collectively, these data indicate that the functional and phenotypic properties of vaccine-induced CD8 T cell populations are sensitive to dose manipulation, yet constrained by epitope specificity in a clonotype-dependent manner.

PMID:
25348625
PMCID:
PMC4238745
DOI:
10.4049/jimmunol.1401017
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center