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AIDS. 2010 Jan 16;24(2):211-5. doi: 10.1097/QAD.0b013e328334442e.

HLA-B molecules target more conserved regions of the HIV-1 proteome.

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  • 1Department of Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands.

Abstract

BACKGROUND:

HLA-B alleles of HIV-infected individuals have been shown to have a major impact on their rate of progression toward AIDS, and the T-cell responses they restrict are immunodominant.

OBJECTIVE:

We sought to identify whether the association of HLA-B alleles with rate of progression toward AIDS is due to targeting of more restricted and thus more conserved regions of the HIV-1 proteome.

METHODS:

Each residue of the HIV-1 consensus subtype B sequence was coded according to the presence/absence of an epitope, using the compiled epitope data available in the HIV-LANL immunology database. The Shannon entropy for each HXB2 position was calculated using pre-aligned HIV-1 clade B sequences as a measure of its degree of conservation. We then compared the entropy of empty versus epitope-containing positions and HLA-B-restricted versus HLA-A-restricted positions.

RESULTS:

Positions containing CD8 epitopes were significantly more conserved than corresponding empty positions. Moreover, residues targeted by HLA-B alleles in the HIV-1 proteome were significantly more conserved than the ones targeted by HLA-A alleles. Analysing a recent dataset, we found that B epitope regions contain significantly more escape mutations and reversions, which might be the reason why we find them to be more conserved.

CONCLUSION:

Our results suggest that epitopes in HIV-1 targeted by HLA-B alleles lie in more constrained regions of its proteins, in which mutations might have a higher fitness cost and tend to revert. Consequently, HLA-B-restricted cytotoxic T-lymphocyte (CTL) responses may persist longer. This may be one of the factors contributing to the immunodominance and impact of HLA-B-restricted CTL responses on disease progression.

[PubMed - indexed for MEDLINE]
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