326 Tools for Searching Optimal CTL Epitopes in Reactive Regions K. Yusim*1, C. Calef1, K. Kommander1, J. J. Szinger1, B. T. Korber1,2 1Los Alamos Natl Lab, NM and 2Santa Fe Inst, NM
Background: The HIV-1 Immunology Database at www.hiv.lanl.gov is a repository of information about HIV-1 T-cell and antibody epitopes, integrated with the sequence variability data from the HIV-1 Sequence Database. The Immunology database includes tables, maps, and alignments of HIV-specific CTL epitopes that are updated through annual summaries of the literature. We also develop simple Web-based tools with the goal of assisting immunologists in experimental design and interpretation of their results.
Methods and Results: Several tools that rely on HLA anchor motif assignments are available to help identify potential CTL epitopes in HIV proteins. A database of HLA binding motifs is stored (updated in Dec 2002) for comparisons to HIV sequences and made as general as possible. The updated HLA binding motif database is a comprehensive summary of the recent literature, and of motif libraries from "The HLA Facts Book" by Marsh, et al. and "MHC Ligands and Peptides Motifs" by Rammensee, et al. We provide 2 tools that search for anchor motifs based on this database. The simplest tool is called "Multiple Motif Scan" and it allows users to find any motif within protein sequences and provides tables of HLA serotypes or genotypes for reference. The second tool, called the Epitope Location Finder (ELF), is specifically intended to help experimentalists identify potential epitopes within a larger reactive peptide. It 1) creates a table of anchor residue motif patterns for related HLA serotypes and genotypes; 2) scans a submitted HIV-1 peptide for potential epitopes based on anchor motifs for a set of specified HLA molecules; 3) finds the HXB2 coordinates of a reactive peptide and extracts the region from our HIV protein alignments; 4) searches our HIV epitope database for all known epitopes within the submitted peptide; 5) maps all HIV proteins, highlighting known epitopes that have HLA presenting molecules related to the HLA type of a reactive individual; and 6) summarizes epitopes that might have been missed because the protein sequence used to design the peptide set differs from known epitopes.
Conclusions: The updated HLA binding motifs database increases utility of the motif scanning tools that are tailored to HIV sequence searches. The tools provide a fast reference for HLA genotype/serotype nomenclature, a resource for interpretation of mutations within epitopes, and a way to narrow the search for optimal epitopes in a reactive region.
