Nonhuman primates are instrumental in research involving Category A-C biodefense pathogens. Cynomolgus macaques (M. Fascicularis) are particularly desireable because they are comparitively inexpensive and widely available. However, little is known about the immunogenetics ot Cynomolgus macaques, complicating the evaluation of pathogen-specific cellular immune responses.
in Specific Aim 1 : Wewill identify at least 60 Major Histocompatibility Complex (MHC) class I and 50 MHC class II molecules expressed by Cynomolgus macaques and develop methods for high-throughput ge- notyping for these alleles. MHC class I and class II alleles may vary among Cynomolgus macaques obtained from different countries, so we will examine the immunogenetics of animals from China, Mauritius, Vietnam, Indonesia, and the Phillipines. More than 12,000 Cynomolgus macaques were imported from these countries in FY2003.
In Specific Aim 2, we will develop preliminary peptide binding motifs for 10common MHC class I and 10 common MHC class II alleles identified in Specific Aim 1. If Cynomolgus macaques from different regions have distinct MHC allele repertoires, we will focus on the definition of peptide binding motifs for alleies found in Chinese, Mauritian, and Vietnamese macaques. More than 75% of the Cynomolgus macaques imported into the United States in FY2003 were brought from one of these countries. The strengths of experienced molecular immunogeneticists and protein biochemists a-e combined in this proposal, enabling the high-throughput characterization of Cynomolgus macaque major histocompatibility complex (MHC) molecules and the pathogen-derived peptides that bind to them. These studies will facilitate the development of species-specific reagents (such as MHC: peptide tetramers) that expand the utility of Cynomolgus macaques in preclinical vaccine trials and studies of disease pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Resource-Related Research Projects (R24)
Project #
3R24RR021745-04S1
Application #
7848659
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Harding, John D
Project Start
2009-07-13
Project End
2011-09-30
Budget Start
2009-07-13
Budget End
2011-09-30
Support Year
4
Fiscal Year
2009
Total Cost
$79,923
Indirect Cost
Name
University of Wisconsin Madison
Department
Veterinary Sciences
Type
Other Domestic Higher Education
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Heimbruch, Katelyn E; Karl, Julie A; Wiseman, Roger W et al. (2015) Novel MHC class I full-length allele and haplotype characterization in sooty mangabeys. Immunogenetics 67:437-45
Karl, Julie A; Heimbruch, Katelyn E; Vriezen, Claire E et al. (2014) Survey of major histocompatibility complex class II diversity in pig-tailed macaques. Immunogenetics 66:613-23
Schafer, Jamie L; Colantonio, Arnaud D; Neidermyer, William J et al. (2014) KIR3DL01 recognition of Bw4 ligands in the rhesus macaque: maintenance of Bw4 specificity since the divergence of apes and Old World monkeys. J Immunol 192:1907-17
Dudley, Dawn M; Karl, Julie A; Creager, Hannah M et al. (2014) Full-length novel MHC class I allele discovery by next-generation sequencing: two platforms are better than one. Immunogenetics 66:15-24
Creager, Hannah M; Becker, Ericka A; Sandman, Kelly K et al. (2011) Characterization of full-length MHC class II sequences in Indonesian and Vietnamese cynomolgus macaques. Immunogenetics 63:611-8
Belisle, Sarah E; Yin, Jiangmei; Shedlock, Devon J et al. (2011) Long-term programming of antigen-specific immunity from gene expression signatures in the PBMC of rhesus macaques immunized with an SIV DNA vaccine. PLoS One 6:e19681
Moreland, Anna J; Guethlein, Lisbeth A; Reeves, R Keith et al. (2011) Characterization of killer immunoglobulin-like receptor genetics and comprehensive genotyping by pyrosequencing in rhesus macaques. BMC Genomics 12:295
Keskin, Derin B; Reinhold, Bruce; Lee, Sun Young et al. (2011) Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens. Front Immunol 2:75
Budde, Melisa L; Wiseman, Roger W; Karl, Julie A et al. (2010) Characterization of Mauritian cynomolgus macaque major histocompatibility complex class I haplotypes by high-resolution pyrosequencing. Immunogenetics 62:773-80
O'Leary, Claire E; Wiseman, Roger W; Karl, Julie A et al. (2009) Identification of novel MHC class I sequences in pig-tailed macaques by amplicon pyrosequencing and full-length cDNA cloning and sequencing. Immunogenetics 61:689-701

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