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

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.

• Authors: Ana I Fontaine Costa, Xiangyu Rao, Emmanuelle Lechenadec, Debbie van Baarle, Can Keşmir
• Journal: AIDS (London, England) (AIDS) Vol. 24 Issue 2 Pg. 211-5 (Jan 16 2010) ISSN: 1473-5571 [Electronic] England
• PMID: 19904197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• HLA-B Antigens
• Immunodominant Epitopes
• Proteome

Topics

• Conserved Sequence
• Disease Progression
• Entropy
• Epitopes, T-Lymphocyte (genetics, immunology)
• HIV Infections (genetics, immunology)
• HIV-1 (genetics)
• HLA-B Antigens (genetics, immunology)
• Humans
• Immunodominant Epitopes (genetics, immunology)
• Proteome (genetics)