Rapid and slow progressors differ by a single MHC class I haplotype in a family of MHC-defined rhesus macaques infected with SIV

David T. Evans, Leslie A. Knapp, Peicheng Jing, Jacque L. Mitchen, Marta Dykhuizen, David C. Montefiori, C. David Pauza, David Watkins

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Highly polymorphic HLA class I molecules may influence rates of disease progression of HIV-infected individuals. Recent evidence suggests that individuals who mount vigorous CTL responses to multiple HIV-1 epitopes have reduced vital loads, and survive longer than individuals that make a less robust or less diverse CTL response. It has been difficult, however, to define associations between particular HLA class I alleles and rates of disease progression. This may be due, in part, to the uncontrolled variables associated with naturally acquired HIV infections. Studies using MHC-defined, non-human primates infected with well characterized viral stocks should help to clarify this relationship. To explore the possibility that MHC class I polymorphism can influence disease progression, we infected four Mamu-DRB- identical individuals from a family of MHC-defined rhesus macaques intravenously with 40 TCID50SIV(mac)239. Two of these macaques developed severe wasting and were euthanized within 80 days of infection, while the other two survived for more than 400 days without showing any symptoms of disease. Since all four of these macaques were Mamu-DRB-identical, we were able to exclude the MHC class II DRB loci as determinant of disease progression. Interestingly, both of the slow progressors made CTL responses to the same three SIV CTL epitopes, which were restricted by two molecules (Mamu-B*03 and B*04) encoded by their common maternal haplotype. The two rapid progressors did not share this haplotype with the slow progressors, and we were unable to detect CTL responses in these two siblings. These observations implicate products of the Mamu-B*03 and B*04 alleles in resistance to disease progression in this family of SIV-infected macaques, and provide additional evidence that certain MHC class I-restricted CTL responses may play a significant role in delaying the onset of AIDS.

Original languageEnglish
Pages (from-to)53-59
Number of pages7
JournalImmunology Letters
Volume66
Issue number1-3
DOIs
StatePublished - Mar 1 1999
Externally publishedYes

Fingerprint

Macaca mulatta
Haplotypes
Disease Progression
Dichlororibofuranosylbenzimidazole
Macaca
Epitopes
Alleles
Primates
HIV Infections
HIV-1
Acquired Immunodeficiency Syndrome
Mothers
HIV
Infection

Keywords

  • CTL
  • MHC
  • Non-human primate

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Rapid and slow progressors differ by a single MHC class I haplotype in a family of MHC-defined rhesus macaques infected with SIV. / Evans, David T.; Knapp, Leslie A.; Jing, Peicheng; Mitchen, Jacque L.; Dykhuizen, Marta; Montefiori, David C.; Pauza, C. David; Watkins, David.

In: Immunology Letters, Vol. 66, No. 1-3, 01.03.1999, p. 53-59.

Research output: Contribution to journalArticle

Evans, David T. ; Knapp, Leslie A. ; Jing, Peicheng ; Mitchen, Jacque L. ; Dykhuizen, Marta ; Montefiori, David C. ; Pauza, C. David ; Watkins, David. / Rapid and slow progressors differ by a single MHC class I haplotype in a family of MHC-defined rhesus macaques infected with SIV. In: Immunology Letters. 1999 ; Vol. 66, No. 1-3. pp. 53-59.
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