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

D. T. Evans, P. Jing, T. M. Allen, D. H. O'Connor, H. Horton, J. E. Venham, M. Piekarczyk, J. Dzuris, M. Dykhuzen, J. Mitchen, R. A. Rudersdorf, C. D. Pauza, A. Sette, R. E. Bontrop, R. DeMars, David Watkins

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7400-7410
Number of pages11
JournalJournal of Virology
Volume74
Issue number16
DOIs
StatePublished - Aug 21 2000
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
major histocompatibility complex
Major Histocompatibility Complex
disease course
epitopes
Disease Progression
Epitopes
lymphocytes
Lymphocytes
cytotoxic T-lymphocytes
Cytotoxic T-Lymphocytes
T-Lymphocyte Epitopes
Haplotypes
haplotypes
Macaca mulatta
Dichlororibofuranosylbenzimidazole
AIDS Vaccines
viruses
loci

ASJC Scopus subject areas

  • Immunology

Cite this

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. / Evans, D. T.; Jing, P.; Allen, T. M.; O'Connor, D. H.; Horton, H.; Venham, J. E.; Piekarczyk, M.; Dzuris, J.; Dykhuzen, M.; Mitchen, J.; Rudersdorf, R. A.; Pauza, C. D.; Sette, A.; Bontrop, R. E.; DeMars, R.; Watkins, David.

In: Journal of Virology, Vol. 74, No. 16, 21.08.2000, p. 7400-7410.

Research output: Contribution to journalArticle

Evans, DT, Jing, P, Allen, TM, O'Connor, DH, Horton, H, Venham, JE, Piekarczyk, M, Dzuris, J, Dykhuzen, M, Mitchen, J, Rudersdorf, RA, Pauza, CD, Sette, A, Bontrop, RE, DeMars, R & Watkins, D 2000, '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', Journal of Virology, vol. 74, no. 16, pp. 7400-7410. https://doi.org/10.1128/JVI.74.16.7400-7410.2000
Evans, D. T. ; Jing, P. ; Allen, T. M. ; O'Connor, D. H. ; Horton, H. ; Venham, J. E. ; Piekarczyk, M. ; Dzuris, J. ; Dykhuzen, M. ; Mitchen, J. ; Rudersdorf, R. A. ; Pauza, C. D. ; Sette, A. ; Bontrop, R. E. ; DeMars, R. ; Watkins, David. / 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. In: Journal of Virology. 2000 ; Vol. 74, No. 16. pp. 7400-7410.
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