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Journal of Virology, August 2000, p. 7400-7410, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Definition of Five New Simian Immunodeficiency Virus Cytotoxic T-Lymphocyte Epitopes and Their Restricting Major Histocompatibility Complex Class I Molecules: Evidence for an Influence on Disease Progression

David T. Evans,1 Peicheng Jing,1 Todd M. Allen,1 David H. O'Connor,1 Helen Horton,1 John E. Venham,1 Marian Piekarczyk,1 John Dzuris,2 Marta Dykhuzen,1 Jacque Mitchen,1 Richard A. Rudersdorf,3 C. David Pauza,1,4 Alessandro Sette,2 Ronald E. Bontrop,5 Robert DeMars,3 and David I. Watkins1,4,*

Wisconsin Regional Primate Research Center,1 Laboratory of Genetics,3 and Department of Pathology and Laboratory Medicine,4 University of Wisconsin, Madison, Wisconsin 53715; Epimmune, Inc., San Diego, California 921212; and Biomedical Primate Research Centre-TNO, 2280 HV Rijswijk, The Netherlands5

Received 27 January 2000/Accepted 15 May 2000

Simian immunodeficiency virus (SIV) infection of the rhesus macaque is currently the best animal model for AIDS vaccine development. One limitation of this model, however, has been the small number of cytotoxic T-lymphocyte (CTL) epitopes and restricting major histocompatibility complex (MHC) class I molecules available for investigating virus-specific CTL responses. To identify new MHC class I-restricted CTL epitopes, we infected five members of a family of MHC-defined rhesus macaques intravenously with SIV. Five new CTL epitopes bound by four different MHC class I molecules were defined. These included two Env epitopes bound by Mamu-A*11 and -B*03 and three Nef epitopes bound by Mamu-B*03, -B*04, and -B*17. All four restricting MHC class I molecules were encoded on only two haplotypes (b or c). Interestingly, resistance to disease progression within this family appeared to be associated with the inheritance of one or both of these MHC class I haplotypes. Two individuals that inherited haplotypes b and c separately survived for 299 and 511 days, respectively, while another individual that inherited both haplotypes survived for 889 days. In contrast, two MHC class I-identical individuals that did not inherit either haplotype rapidly progressed to disease (survived <80 days). Since all five offspring were identical at their Mamu-DRB loci, MHC class II differences are unlikely to account for their patterns of disease progression. These results double the number of SIV CTL epitopes defined in rhesus macaques and provide evidence that allelic differences at the MHC class I loci may influence rates of disease progression among AIDS virus-infected individuals.

* Corresponding author. Mailing address: Wisconsin Regional Primate Research Center, 1220 Capitol Ct., Madison, WI 53715-1299. Phone: (608) 265-3380. Fax: (608) 265-8084. E-mail: watkins{at}primate.wisc.edu.

Journal of Virology, August 2000, p. 7400-7410, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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