MHC TYPING OF MACAQUES USED IN AIDS RESEARCH

University Of Wisconsin-Madison, Madison WI

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To offer MHC typing of the MHC class I and II loci for investigators working with macaques (Indian rhesus, Chinese rhesus, and Cynomolgus). To adapt technologies for HLA typing to molecular typing of macaque (Indian rhesus, Chinese rhesus, and Cynomolgus) MHC class I and II. The increased utility of various species of macaques as animal models in both HIV vaccine development and pathogenesis studies necessitates the continuation of reference MHC typing laboratories for these species. We plan to continue to offer services to both the North American and European scientific communities for MHC typing of macaques. Initially, this will include PCR-SSP tests for alleles encoding MHC class I and II molecules that bind peptides derived from SIV and SHIV. We are developing additional molecular techniques for analysis of the Indian rhesus and Chinese rhesus and Cynomolgus macaque MHC class I and class II alleles. Additionally, we offer training and materials to individual laboratories that wish to set up MHC typing. Finally, we are developing a panel of well-characterized cell lines that will be invaluable for the analysis of the MHC in the macaque. Since 2002 to the present, we have performed over 126,000 typings for over 130 investigators at 50 institutions. In 2009, we have conducted 21,800 typings at the request of 23 principal investigators from 19 different institutions. We are preparing to offer expanded Class II typing services during 2010. This research used WNPRC Immunogenetics &Virology Services. PUBLICATIONS: Doxiadis GG, Heijmans CM, Bonhomme M, Otting N, Crouau-Roy B, Bontrop RE. Compound evolutionary history of the rhesus macaque MHC class I B region revealed by microsatellite analysis and localization of retroviral sequences. PLoS One. 2009;4(1):e4287. PMID: 19172173 Wilson NA, Keele BF, Reed JS, Piaskowski SM, MacNair CE, Bett AJ, Liang X, Wang F, Thoryk E, Heidecker GJ, Citron MP, Huang L, Lin J, Vitelli S, Ahn CD, Kaizu M, Maness NJ, Reynolds MR, Friedrich TC, Loffredo JT, Rakasz EG, Erickson S, Allison DB, Piatak M Jr, Lifson JD, Shiver JW, Casimiro DR, Shaw GM, Hahn BH, Watkins DI. Vaccine-induced cellular responses control simian immunodeficiency virus replication after heterologous challenge. J Virol. 2009 Jul;83(13):6508-21. PMID: 19403685 Loffredo JT, Sidney J, Bean AT, Beal DR, Bardet W, Wahl A, Hawkins OE, Piaskowski S, Wilson NA, Hildebrand WH, Watkins DI, Sette A. 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. 2009 Jun 15;182(12):7763-75. PMID: 19494300 Valentine LE, Loffredo JT, Bean AT, Le[unreadable]n EJ, MacNair CE, Beal DR, Piaskowski SM, Klimentidis YC, Lank SM, Wiseman RW, Weinfurter JT, May GE, Rakasz EG, Wilson NA, Friedrich TC, O'Connor DH, Allison DB, Watkins DI. Infection with "escaped" virus variants impairs control of simian immunodeficiency virus SIVmac239 replication in Mamu-B*08-positive macaques. J Virol. 2009 Nov;83(22):11514-27. Sep 2.PMID: 19726517 Vojnov L, Reed JS, Weisgrau KL, Rakasz EG, Loffredo JT, Piaskowski SM, Sacha JB, Kolar HL, Wilson NA, Johnson RP, Watkins DI. Effective simian immunodeficiency virus-specific CD8+ T cells lack an easily detectable, shared characteristic. J Virol. 2010 Jan;84(2):753-64.PMID: 19889785 Otting N, Doxiadis GG, Bontrop RE. Definition of Mafa-A and -B haplotypes in pedigreed cynomolgus macaques (Macaca fascicularis). Immunogenetics. 2009 Nov 24. PMID: 19937015 de Groot NG, Heijmans CM, de Groot N, Doxiadis GG, Otting N, Bontrop RE. The chimpanzee Mhc-DRB region revisited: gene content, polymorphism, pseudogenes, and transcripts. Mol Immunol. 2009 Dec;47(2-3):381-9. PMID: 19800692 Hessell AJ, Rakasz EG, Tehrani DM, Huber M, Weisgrau KL, Landucci G, Forthal DN, Koff WC, Poignard P, Watkins DI, Burton DR. Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. J Virol. 2010 Feb;84(3):1302-13. PMID: 19906907