Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Dec 15;200(12):1825-33.
doi: 10.1086/648401.

Conserved HIV-1 epitopes continuously elicit subdominant cytotoxic T-lymphocyte responses

Yi Liu  1 , John McNevin, Morgane Rolland, Hong Zhao, Wenjie Deng, Janine Maenza, Claire E Stevens, Ann C Collier, M Juliana McElrath, James I Mullins
Affiliations

Conserved HIV-1 epitopes continuously elicit subdominant cytotoxic T-lymphocyte responses

Yi Liu et al. J Infect Dis. .

Abstract

Background: The epitope specificities and antiviral activities of class I HLA-restricted CD8(+) T cells, especially those induced during human immunodeficiency virus type 1 (HIV-1) primary infection, are important considerations in designing HIV-1 vaccines. Conserved epitopes may be more commonly and persistently recognized than variable epitopes, as they may be more likely to be present in infecting viruses. However, some studies have shown preferential or similar targeting of variable versus conserved epitopes during primary infection.

Methods: We analyzed cytotoxic T-lymphocyte (CTL) responses toward predefined conserved and variable epitopes in 45 subjects during primary (n = 34) and/or chronic infection (n = 16).

Results: Conserved and variable CTL epitopes were recognized with similar probabilities, whereas conserved epitopes generally elicited subdominant responses during both primary and chronic infection. During primary infection, CTL responses against Gag versus responses against Env and variable epitopes tended to be associated with lower and higher viral loads, respectively. During chronic infection, Env-specific responses tended to be associated with lower CD4(+) cell counts.

Conclusions: Subdominant CTL recognition of conserved HIV-1 epitopes commonly occurs from the primary through chronic stages of HIV-1 infection. These findings underscore the challenge in designing T cell-based vaccines that can induce immunodominant CTL responses to conserved HIV-1 regions.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest: none reported.

Figures

Figure 1
Figure 1
Numbers of HIV-1 epitopes tested and recognized. Black bars represent epitopes tested and gray bars represent epitopes recognized. A and B) all epitopes, C and D) conserved epitopes, E and F) variable epitopes during primary and chronic infection, respectively.
Figure 2
Figure 2
Epitopes commonly recognized during A) primary and B) chronic infection. Only those epitopes that were tested in more than five subjects and were recognized in more than half of the tested subjects were evaluated. Black bars represent the number of subjects tested and gray bars represent the number of subjects that recognized the epitope. White bars represent the number of subjects with an immunodominant response to the epitope. The right panel lists the commonly recognized epitopes and their database frequencies. For HLA B7, the four epitopes listed were recognized by same number of subjects, and the epitope found to elicit immunodominant CTL responses is labeled with *. Thus, only single gray and white bars are presented for B7.
Figure 3
Figure 3
Maximum and median magnitudes of CTL responses to conserved and variable HIV-1 epitopes within subjects. A and B) comparison of the maximum magnitudes, C and D) comparison of the median magnitudes of CTL responses to conserved and variable epitopes during primary and chronic infection. Each line represents results from an individual subject. The symbols were highlighted red when the within-subject dominant CTL responses were elicited by conserved epitopes. The horizontal bars represent the mean for each data set. Only data from the first time point are presented if chronic CTL responses were measured at two time points. In one subject, the dominant CTL response elicited by a conserved epitope (the A26-restricted EVIPMFSAL) was observed at the second time point measurement, and is thus not presented in the figure.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB. Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol. 1994;68:6103–6110. - PMC - PubMed
    1. Koup RA, Safrit JT, Cao Y, et al. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol. 1994;68:4650–5. - PMC - PubMed
    1. Musey L, Hughes J, Schacker T, Shea T, Corey L, McElrath MJ. Cytotoxic-T-cell responses, viral load, and disease progression in early human immunodeficiency virus type 1 infection. N Engl J Med. 1997;337:1267–74. - PubMed
    1. Jones NA, Wei X, Flower DR, et al. Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response. J Exp Med. 2004;200:1243–56. - PMC - PubMed
    1. Allen TM, Altfeld M, Geer SC, et al. Selective escape from CD8+ T-cell responses represents a major driving force of human immunodeficiency virus type 1 (HIV-1) sequence diversity and reveals constraints on HIV-1 evolution. J Virol. 2005;79:13239–49. - PMC - PubMed

Publication types

Substances