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Jacobs ES, Persad D, Ran L, et al. A CD4+ T cell antagonist epitope down-regulates activating signaling proteins, up-regulates inhibitory signaling proteins and abrogates HIV-specific T cell function. Retrovirology. 2014;11:57doi: 10.1186/1742-4690-11-57.
Jacobs, E. S., Persad, D., Ran, L., Danesh, A., Heitman, J. W., Deng, X., Cameron, M. J., Kelvin, D. J., & Norris, P. J. (2014). A CD4+ T cell antagonist epitope down-regulates activating signaling proteins, up-regulates inhibitory signaling proteins and abrogates HIV-specific T cell function. Retrovirology, 1157. https://doi.org/10.1186/1742-4690-11-57
Jacobs, Evan S, et al. "A CD4+ T cell antagonist epitope down-regulates activating signaling proteins, up-regulates inhibitory signaling proteins and abrogates HIV-specific T cell function." Retrovirology vol. 11 (2014): 57. doi: https://doi.org/10.1186/1742-4690-11-57
Jacobs ES, Persad D, Ran L, Danesh A, Heitman JW, Deng X, Cameron MJ, Kelvin DJ, Norris PJ. A CD4+ T cell antagonist epitope down-regulates activating signaling proteins, up-regulates inhibitory signaling proteins and abrogates HIV-specific T cell function. Retrovirology. 2014 Jul 05;11:57. doi: 10.1186/1742-4690-11-57. PMID: 24996903; PMCID: PMC4227135.
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Retrovirology. 2014 Jul 05;11:57. doi: 10.1186/1742-4690-11-57.

A CD4+ T cell antagonist epitope down-regulates activating signaling proteins, up-regulates inhibitory signaling proteins and abrogates HIV-specific T cell function.

Retrovirology

Evan S Jacobs, Desmond Persad, Longsi Ran, Ali Danesh, John W Heitman, Xutao Deng, Mark J Cameron, David J Kelvin, Philip J Norris

Affiliations

  1. Blood Systems Research Institute, San Francisco, California. [email protected].

PMID: 24996903 PMCID: PMC4227135 DOI: 10.1186/1742-4690-11-57

Abstract

BACKGROUND: CD4+ T cells are critically important in HIV infection, being both the primary cells infected by HIV and likely playing a direct or indirect role in helping control virus replication. Key areas of interest in HIV vaccine research are mechanisms of viral escape from the immune response. Interestingly, in HIV infection it has been shown that peptide sequence variation can reduce CD4+ T cell responses to the virus, and small changes to peptide sequences can transform agonist peptides into antagonist peptides.

RESULTS: We describe, at a molecular level, the consequences of antagonism of HIV p24-specific CD4+ T cells. Antagonist peptide exposure in the presence of agonist peptide caused a global suppression of agonist-induced gene expression and signaling molecule phosphorylation. In addition to down-regulation of factors associated with T cell activation, a smaller subset of genes associated with negative regulation of cell activation was up-regulated, including KFL-2, SOCS-1, and SPDEY9P. Finally, antagonist peptide in the absence of agonist peptide also delivered a negative signal to T cells.

CONCLUSIONS: Small changes in p24-specific peptides can result in T cell antagonism and reductions of both T cell receptor signaling and activation. These changes are at least in part mediated by a dominant negative signal delivered by antagonist peptide, as evidenced by up-regulation of negative regulatory genes in the presence of agonist plus antagonist stimulation. Antagonism can have dramatic effects on CD4+ T cell function and presents a potential obstacle to HIV vaccine development.

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