Next Article in Journal
MmpL Proteins in Physiology and Pathogenesis of M. tuberculosis
Previous Article in Journal
Microbial Population Changes and Their Relationship with Human Health and Disease
Open AccessArticle

Defining Kinetic Properties of HIV-Specific CD8+ T-Cell Responses in Acute Infection

by Yiding Yang 1 and Vitaly V. Ganusov 1,2,3,*
1
Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA
2
National Institute for Mathematical and Biological Synthesis, University of Tennessee, Knoxville, TN 37996, USA
3
Department of Mathematics, University of Tennessee, Knoxville, TN 37996, USA
*
Author to whom correspondence should be addressed.
Microorganisms 2019, 7(3), 69; https://doi.org/10.3390/microorganisms7030069
Received: 5 January 2019 / Revised: 22 February 2019 / Accepted: 24 February 2019 / Published: 4 March 2019
(This article belongs to the Section Medical Microbiology)
Multiple lines of evidence indicate that CD8 + T cells are important in the control of HIV-1 (HIV) replication. However, CD8 + T cells induced by natural infection cannot eliminate the virus or reduce viral loads to acceptably low levels in most infected individuals. Understanding the basic quantitative features of CD8 + T-cell responses induced during HIV infection may therefore inform us about the limits that HIV vaccines, which aim to induce protective CD8 + T-cell responses, must exceed. Using previously published experimental data from a cohort of HIV-infected individuals with sampling times from acute to chronic infection we defined the quantitative properties of CD8 + T-cell responses to the whole HIV proteome. In contrast with a commonly held view, we found that the relative number of HIV-specific CD8 + T-cell responses (response breadth) changed little over the course of infection (first 400 days post-infection), with moderate but statistically significant changes occurring only during the first 35 symptomatic days. This challenges the idea that a change in the T-cell response breadth over time is responsible for the slow speed of viral escape from CD8 + T cells in the chronic infection. The breadth of HIV-specific CD8 + T-cell responses was not correlated with the average viral load for our small cohort of patients. Metrics of relative immunodominance of HIV-specific CD8 + T-cell responses such as Shannon entropy or the Evenness index were also not significantly correlated with the average viral load. Our mathematical-model-driven analysis suggested extremely slow expansion kinetics for the majority of HIV-specific CD8 + T-cell responses and the presence of intra- and interclonal competition between multiple CD8 + T-cell responses; such competition may limit the magnitude of CD8 + T-cell responses, specific to different epitopes, and the overall number of T-cell responses induced by vaccination. Further understanding of mechanisms underlying interactions between the virus and virus-specific CD8 + T-cell response will be instrumental in determining which T-cell-based vaccines will induce T-cell responses providing durable protection against HIV infection. View Full-Text
Keywords: acute HIV infection; vaccines; CD8+ T cells; immune response; multiple epitopes; competition; mathematical model acute HIV infection; vaccines; CD8+ T cells; immune response; multiple epitopes; competition; mathematical model
Show Figures

Figure 1

MDPI and ACS Style

Yang, Y.; Ganusov, V.V. Defining Kinetic Properties of HIV-Specific CD8+ T-Cell Responses in Acute Infection. Microorganisms 2019, 7, 69.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop