AI Article Synopsis
- CD4(+) helper T cells play a key role in managing HIV-1 viremia, but current vaccines aren't very effective due to the virus's genetic variability and the structure of its envelope protein.
- Researchers attempted to improve immune responses by altering the three-dimensional structure of the HIV envelope protein gp120 by deleting three disulfide bonds, aiming to boost weakly immunogenic epitopes.
- However, when they immunized mice with these modified variants, they found that the overall CD4(+) T-cell response decreased, but one variant did lead to higher antibody levels with strong CD4-blocking capability.
Article Abstract
CD4(+) helper T cells specific for human immunodeficiency virus type 1 (HIV-1) are associated with control of viremia. Nevertheless, vaccines have had limited effectiveness thus far, in part because sequence variability and other structural features of the HIV envelope glycoprotein deflect the immune response. Previous studies indicated that CD4(+) T-cell epitope dominance is controlled by antigen three-dimensional structure through its influence on antigen processing and presentation. In this work, three disulfide bonds in the outer domain of gp120 were individually deleted in order to destabilize the local three-dimensional structure and enhance the presentation of nearby weakly immunogenic epitopes. However, upon immunization of groups of BALB/c mice, the CD4(+) T-cell response was broadly reduced for all three variants, and distinct epitope profiles emerged. For one variant, antibody titers were sharply increased, and the antibody exhibited significant CD4-blocking activity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838136 | PMC |
| http://dx.doi.org/10.1128/JVI.02242-09 | DOI Listing |
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