This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Burwitz, B. J.
Right arrow Articles by O'Connor, D. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Burwitz, B. J.
Right arrow Articles by O'Connor, D. H.

 Previous Article  |  Next Article 

Journal of Virology, June 2009, p. 6011-6019, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.00199-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Mauritian Cynomolgus Macaques Share Two Exceptionally Common Major Histocompatibility Complex Class I Alleles That Restrict Simian Immunodeficiency Virus-Specific CD8+ T Cells{triangledown} ,{dagger}

Benjamin J. Burwitz,1 Chad J. Pendley,2 Justin M. Greene,1 Ann M. Detmer,2 Jennifer J. Lhost,1 Julie A. Karl,2 Shari M. Piaskowski,1 Richard A. Rudersdorf,1 Lyle T. Wallace,1 Benjamin N. Bimber,1 John T. Loffredo,1 Daryl G. Cox,3 Wilfried Bardet,3 William Hildebrand,3 Roger W. Wiseman,2 Shelby L. O'Connor,1 and David H. O'Connor1,2*

Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin 53706,1 Wisconsin National Primate Research Center, Madison, Wisconsin 53706,2 Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 731043

Received 27 January 2009/ Accepted 25 March 2009

Vaccines that elicit CD8+ T-cell responses are routinely tested for immunogenicity in nonhuman primates before advancement to clinical trials. Unfortunately, the magnitude and specificity of vaccine-elicited T-cell responses are variable in currently utilized nonhuman primate populations, owing to heterogeneity in major histocompatibility (MHC) class I genetics. We recently showed that Mauritian cynomolgus macaques (MCM) have unusually simple MHC genetics, with three common haplotypes encoding a shared pair of MHC class IA alleles, Mafa-A*25 and Mafa-A*29. Based on haplotype frequency, we hypothesized that CD8+ T-cell responses restricted by these MHC class I alleles would be detected in nearly all MCM. We examine here the frequency and functionality of these two alleles, showing that 88% of MCM express Mafa-A*25 and Mafa-A*29 and that animals carrying these alleles mount three newly defined simian immunodeficiency virus-specific CD8+ T-cell responses. The epitopes recognized by each of these responses accumulated substitutions consistent with immunologic escape, suggesting these responses exert antiviral selective pressure. The demonstration that Mafa-A*25 and Mafa-A*29 restrict CD8+ T-cell responses that are shared among nearly all MCM indicates that these animals are an advantageous nonhuman primate model for comparing the immunogenicity of vaccines that elicit CD8+ T-cell responses.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Dr., Madison, WI 53711. Phone: (608) 265-3389. Fax: (608) 265-8084. E-mail: doconnor{at}primate.wisc.edu

{triangledown} Published ahead of print on 1 April 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, June 2009, p. 6011-6019, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.00199-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Willer, D. O., Guan, Y., Luscher, M. A., Li, B., Pilon, R., Fournier, J., Parenteau, M., Wainberg, M. A., Sandstrom, P., MacDonald, K. S. (2010). Multi-Low-Dose Mucosal Simian Immunodeficiency Virus SIVmac239 Challenge of Cynomolgus Macaques Immunized with "Hyperattenuated" SIV Constructs. J. Virol. 84: 2304-2317 [Abstract] [Full Text]  
  • Beignon, A.-S., Mollier, K., Liard, C., Coutant, F., Munier, S., Riviere, J., Souque, P., Charneau, P. (2009). Lentiviral Vector-Based Prime/Boost Vaccination against AIDS: Pilot Study Shows Protection against Simian Immunodeficiency Virus SIVmac251 Challenge in Macaques. J. Virol. 83: 10963-10974 [Abstract] [Full Text]  
  • Bimber, B. N., Burwitz, B. J., O'Connor, S., Detmer, A., Gostick, E., Lank, S. M., Price, D. A., Hughes, A., O'Connor, D. (2009). Ultradeep Pyrosequencing Detects Complex Patterns of CD8+ T-Lymphocyte Escape in Simian Immunodeficiency Virus-Infected Macaques. J. Virol. 83: 8247-8253 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»