HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sidney, J. Articles by Sette, A. Search for Related Content PubMed PubMed Citation Articles by Sidney, J. Articles by Sette, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB GLUTAMIC ACID HYDROCHLORIDE

Simultaneous Prediction of Binding Capacity for Multiple Molecules of the HLA B44 Supertype ¹

John Sidney^*, Scott Southwood, Valerie Pasquetto^* and Alessandro Sette^2,*

^* Division of Translational Immunology and Biodefense, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; and Epimmune Inc., San Diego, CA 92121

We selected for study a set of B44-supertype molecules collectively represented in >40% of the individuals in all major ethnicities (B*1801, B*4001, B*4002, B*4402, B*4403, and B*4501). The peptide-binding specificity of each molecule was characterized using single amino acid substitution analogues and nonredundant peptide libraries. In all cases, only peptide ligands with glutamic acid in position 2 were preferred. At the C terminus, each allele was associated with a unique but broad pattern of preferences, but all molecules tolerated hydrophobic/aliphatic (leucine, isoleucine, valine, methionine), aromatic (tyrosine, phenylalanine, tryptophan), and small (alanine, glycine, threonine) residues. Secondary anchor motifs were also defined for all molecules. Together, these features were used to define a B44 supermotif and a novel algorithm for calculating degeneracy scores that can be used to predict B44-supertype degenerate binders. Approximately 90% of the peptides with a B44 supermotif degeneracy score of >10 bound at least three of the six B44-supertype molecules studied with high affinity. Finally, a number of peptides derived from hepatitis B and C viruses, HIV, and Plasmodium falciparum have been identified that have degenerate B44 supertype-binding capacity. Taken together, these findings have important implications for epitope-based approaches to vaccination, immunotherapy, and the monitoring of immune responses.

This article has been cited by other articles:

				J. T. Loffredo, J. Sidney, A. T. Bean, D. R. Beal, W. Bardet, A. Wahl, O. E. Hawkins, S. Piaskowski, N. A. Wilson, W. H. Hildebrand, et al. Two MHC Class I Molecules Associated with Elite Control of Immunodeficiency Virus Replication, Mamu-B*08 and HLA-B*2705, Bind Peptides with Sequence Similarity J. Immunol., June 15, 2009; 182(12): 7763 - 7775. [Abstract] [Full Text] [PDF]

				S. M. Mueller, B. Schaetz, K. Eismann, S. Bergmann, M. Bauerle, M. Schmitt-Haendle, H. Walter, B. Schmidt, K. Korn, H. Sticht, et al. Dual Selection Pressure by Drugs and HLA Class I-Restricted Immune Responses on Human Immunodeficiency Virus Type 1 Protease J. Virol., March 15, 2007; 81(6): 2887 - 2898. [Abstract] [Full Text] [PDF]

				V. Thammavongsa, G. Raghuraman, T. M. Filzen, K. L. Collins, and M. Raghavan HLA-B44 Polymorphisms at Position 116 of the Heavy Chain Influence TAP Complex Binding via an Effect on Peptide Occupancy. J. Immunol., September 1, 2006; 177(5): 3150 - 3161. [Abstract] [Full Text] [PDF]

				P. Donnes and O. Kohlbacher SVMHC: a server for prediction of MHC-binding peptides. Nucleic Acids Res., July 1, 2006; 34(Web Server issue): W194 - W197. [Abstract] [Full Text] [PDF]