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Kinetics of Expansion of Epitope-Specific T Cell Responses during Primary HIV-1 Infection¹

Emma L. Turnbull^2,*, MaiLee Wong^*, Shuyi Wang, Xiping Wei, Nicola A. Jones^*, Karen E. Conrod^*, Diana Aldam, Jo Turner, Pierre Pellegrino, Brandon F. Keele, Ian Williams, George M. Shaw and Persephone Borrow^*

^* Viral Immunology Group, Jenner Institute, University of Oxford, Compton, United Kingdom; Departments of Medicine and Microbiology, University of Alabama, Birmingham, AL 35294; and Centre for Sexual Health and HIV Research, Mortimer Market Centre, London, United Kingdom

Multiple lines of evidence support a role for CD8⁺ T cells in control of acute/early HIV replication; however, features of the primary HIV-specific CD8⁺ T cell response that may impact on the efficiency of containment of early viral replication remain poorly defined. In this study, we performed a novel, comprehensive analysis of the kinetics of expansion of components of the HIV-specific CD8⁺ T cell response in 21 acutely infected individuals. Epitope-specific T cell responses expanded asynchronously during primary infection in all subjects. The most rapidly expanded responses peaked as early as 5 days following symptomatic presentation and were typically of very limited epitope breadth. Responses of additional specificities expanded and contracted in subsequent waves, resulting in successive shifts in the epitope immunodominance hierarchy over time. Sequence variation and escape were temporally associated with the decline in magnitude of only a subset of T cell responses, suggesting that other factors such as Ag load and T cell exhaustion may play a role in driving the contraction of HIV-specific T cell responses. These observations document the preferential expansion of CD8⁺ T cells recognizing a subset of epitopes during the viral burst in acute HIV-1 infection and suggest that the nature of the initial, very rapidly expanded T cell response may influence the efficiency with which viral replication is contained in acute/early HIV infection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Grand Challenges in Global Health Program of the Bill and Melinda Gates Foundation (No. 37874), and by core funding from Jenner Institute. P.B. received salary support from a Senior Jenner Fellowship, and is a Jenner Institute investigator.

² Address correspondence and reprint requests to Dr. Emma L. Turnbull, Jenner Institute, University of Oxford, Compton, Newbury, Berkshire RG20 7NN, U.K. E-mail address: emma.turnbull{at}jenner.ac.uk

³ Abbreviations used in this paper: DFOSx, days following the onset of symptoms; FOSx, following the onset of symptoms.

⁴ The online version of this article contains supplemental material.