AIDSWEEKLY Plus; Monday, July 14, 2003
Michael Greer, Senior Medical Writer

"The antigenic diversity" of HIV "represents a significant challenge for vaccine design as well as the comprehensive assessment of HIV-1-specific immune responses in infected persons," explained Marcus Altfeld and colleagues at Harvard Medical School in Boston, the Allegheny-Singer Research Institute in Pittsburgh, the University of Washington in Seattle, Los Alamos National Laboratory in Los Alamos, New Mexico, and the University of Oxford in Oxford, England.

Often, virus-specific T-cell responses could only be detected with immunoassays using autologous viral peptides, Altfeld and coauthors found.

The researchers evaluated T-cell activity against a variety of HIV Gag, Tat, and Vpr peptides in six patients using a gamma interferon Elispot assay. Almost a third of the peptides targeted by T cells could only be detected when autologous viral sequences were used in place of the standard clade B consensus sequence, they said.

In addition, significantly more potent Tat- and Vpr-specific T-cell responses were detected when autologous peptide reagents were used, according to the report. These regulatory and accessory proteins are considerably more variable than their counterparts.

Other experiments showed that the average intra-peptide amino acid variability was inversely correlated to the frequency at which the peptide was recognized by T cells (Enhanced detection of human immunodeficiency virus type 1-specific T-cell responses to highly variable regions by using peptides based on autologous virus sequences. J Virol. 2003 Jul;77(13):7330-40.

These results "indicate that accurate assessment of T-cell responses directed against the more variable regulatory and accessory HIV-1 proteins requires reagents based on autologous virus sequences," Altfeld and colleagues concluded. "They also demonstrate that CD8 T-cell responses to the variable HIV-1 proteins are more common than previously reported."

The corresponding author for this report is Marcus Altfeld, MGH-East, CNY 5212, 149 13th St., Charlestown, MA 02129, USA. E-mail: maltfeld@partners.org.

Key points reported in this study include:

1) Reagents based on autologous HIV peptides are needed for accurate measurement of antiviral T-cell activity

2) Almost a third of HIV Gag, Tat and Vpr peptides targeted by T cells were only detectable using autologous peptide reagents

3) The use of autologous reagents also showed that T-cell responses to the highly variable Tat and Vpr proteins were much stronger than previously thought.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Altfeld M, Addo MM, Shankarappa R, et al., "Enhanced detection of human immunodeficiency virus type 1-specific T-cell responses to highly variable regions by using peptides based on autologous virus sequences", J Virol. 2003 Jul;77(13):7330-40

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