Email updates

Keep up to date with the latest news and content from Immunome Research and BioMed Central.

Open Access Research

In silico characterization of immunogenic epitopes presented by HLA-Cw*0401

Joo Chuan Tong1, Zong Hong Zhang1, J Thomas August3, Vladimir Brusic4, Tin Wee Tan2 and Shoba Ranganathan25*

Author Affiliations

1 Institute for Infocomm Research, 21 Heng Mui Keng Terrace, 119613, Singapore

2 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117597, Singapore

3 Department of Pharmacology and Molecular Sciences, John Hopkins University School of Medicine, Baltimore, MD, USA

4 Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA, USA

5 Department of Chemistry and Biomolecular Sciences & Biotechnology Research Institute, Macquarie University, NSW 2109, Australia

For all author emails, please log on.

Immunome Research 2007, 3:7  doi:10.1186/1745-7580-3-7

Published: 20 August 2007

Abstract

Background

HLA-C locus products are poorly understood in part due to their low expression at the cell surface. Recent data indicate that these molecules serve as major restriction elements for human immunodeficiency virus type 1 (HIV-1) cytotoxic T lymphocyte (CTL) epitopes. We report here a structure-based technique for the prediction of peptides binding to Cw*0401. The models were rigorously trained, tested and validated using experimentally verified Cw*0401 binding and non-binding peptides obtained from biochemical studies. A new scoring scheme facilitates the identification of immunological hot spots within antigens, based on the sum of predicted binding energies of the top four binders within a window of 30 amino acids.

Results

High predictivity is achieved when tested on the training (r2 = 0.88, s = 3.56 kJ/mol, q2 = 0.84, spress = 5.18 kJ/mol) and test (AROC = 0.93) datasets. Characterization of the predicted Cw*0401 binding sequences indicate that amino acids at key anchor positions share common physico-chemical properties which correlate well with existing experimental studies.

Conclusion

The analysis of predicted Cw*0401-binding peptides showed that anchor residues may not be restrictive and the Cw*0401 binding pockets may possibly accommodate a wide variety of peptides with common physico-chemical properties. The potential Cw*0401-specific T-cell epitope repertoires for HIV-1 p24gag and gp160gag glycoproteins are well distributed throughout both glycoproteins, with thirteen and nine immunological hot spots for HIV-1 p24gag and gp160gag glycoproteins respectively. These findings provide new insights into HLA-C peptide selectivity, indicating that pre-selection of candidate HLA-C peptides may occur at the TAP level, prior to peptide loading in the endoplasmic reticulum.