BCB '11 Proceedings of the 2nd ACM Conference on Bioinformatics, Computational Biology and Biomedicine Pages 602-606 PRED mafa : a system for prediction of peptide binding to several MHC class I molecules in cynomolgus macaques Guang Lan Zhang Cancer Vaccine Center, Dana-Farber Cancer Institute HIM 418, 77 Avenue Louis Pasteur Boston, MA 02115 1-617-582-7951 guanglan_zhang@dfci.harvard.edu David H. O’Connor Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison Wisconsin, 53706 1-608-890-0845 doconnor@primate.wisc.edu Melisa L. Budde Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison Wisconsin, 53706 1-608-890-0845 mlbudde@wisc.edu William H. Hildebrand Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, 73104 1-405-271-1203 william-hildebrand@ouhsc.edu Jennifer J. Lhost Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison Wisconsin, 53706 1-608-890-0845 jjlhost@gmail.com Vladimir Brusic Cancer Vaccine Center, Dana-Farber Cancer Institute HIM 418, 77 Avenue Louis Pasteur Boston, MA 02115 1-617-632-3824 vladimir_brusic@dfci.harvard.edu ABSTRACT PRED mafa is a computational system for prediction of peptide binding to three transcriptionally abundant major histocompatibility complex (MHC) class I alleles of Mauritian cynomolgus macaque, an important animal model for the study of human disease. The prediction system utilizes quantitative matrices, which were validated using experimentally determined binders and supported by in vivo studies. We developed 8-mer and 9-mer prediction matrices for Mafa-A1*063:02, 9-mer, 10- mer, and 11-mer prediction matrices for Mafa-B*011:01, and a 9- mer prediction matrix for Mafa-B*075:01. PRED mafa is available at http://cvc.dfci.harvard.edu/mafa/. Categories and Subject Descriptors J.3 [COMPUTER APPLICATIONS]: Life and Medical Sciences – nonhuman primates, SIV, MHC binding peptide. General Terms Algorithms, Performance, Design. Keywords Mauritian cynomolgus macaques, SIV, HIV, major histocompatibility complex, MHC, vaccine design, online prediction system. 1. INTRODUCTION Vaccines are routinely tested for immunogenicity in nonhuman primates (NHP) before advancement to clinical trials. For example. simian immunodeficiency virus (SIV)-infected NHP are considered the best animal models for preclinical studies of human immunodeficiency virus (HIV) vaccines [9]. Rhesus macaques (Macaca mulatta) are well-established models for studying human disease pathogenesis and vaccine development. Acute shortages of rhesus macaques caused by the 1978 ban on export of macaques from India slowed down research on human diseases. Another type of NHP model, cynomolgus macaque (Macaca fascicularis), became frequently used for infectious disease and transplantation research. The A and B locus molecules of MHC region in rhesus and cynomolgus macaques are quite different from their human counterparts with little conservation of allelic lineages between macaques and humans [10]. MHC class I expression in macaques is significantly more complex than in humans. Human MHC class I loci are well defined with only three classical polymorphic genes per haplotype (HLA-A, -B, and -C). Macaques can have a heterogeneous assortment of up to 20 MHC class I loci per haplotype [8]. CD8 + T cells control viral infection through direct cytolysis of infected cells and through production of soluble antiviral mediators. This function is mediated by recognition of linear peptide epitopes presented by MHC class I molecules. The recognition of a given antigenic peptide by the immune system of an individual depends on the peptide’s ability to bind one or more of the host MHC. A significant research effort has been focused on study of a single well-defined NHP MHC allele, Mamu- A1*001. To date, approximately 20 NHP MHC alleles have been reported to mediate CD8 + responses against SIV [3,7]. Among them, four Mafa (M. fascicularis MHC) alleles, Mafa-A1*004:01, -A1*063:02, -A4*01:01, and -B*104:01, were reported to restrict CD8 + T cell responses. Mauritian cynomolgus macaques (MCM) are descended from a small population geographically isolated over the last 500 years [6]. They have a relatively simple, as compared to other macaques, MHC genetics consisting of seven major haplotypes, termed M1 to M7. In this paper, we present predictive scoring matrices for prediction of peptide binding to three most frequent class I alleles within the M3 haplotype: Mafa-A1*063:02, - B*011:01, and -B*075:01. These three molecules are transcriptionally abundant class I alleles reported to be largely responsible for restricting SIV-specific CD8+ T cell responses