Document Detail

Rapid and slow progressors differ by a single MHC class I haplotype in a family of MHC-defined rhesus macaques infected with SIV.
MedLine Citation:
PMID:  10203034     Owner:  NLM     Status:  MEDLINE    
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 viral 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 TCID50SIVmac239. 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.
D T Evans; L A Knapp; P Jing; J L Mitchen; M Dykhuizen; D C Montefiori; C D Pauza; D I Watkins
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Immunology letters     Volume:  66     ISSN:  0165-2478     ISO Abbreviation:  Immunol. Lett.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-06-01     Completed Date:  1999-06-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7910006     Medline TA:  Immunol Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  53-9     Citation Subset:  IM; X    
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison 53715, USA.
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MeSH Terms
Amino Acid Sequence
Cell Line
Disease Progression
Epitopes, T-Lymphocyte / immunology
Gene Products, env / immunology
Gene Products, nef / immunology
Histocompatibility Antigens Class I / immunology*
Macaca mulatta
Molecular Sequence Data
Simian Acquired Immunodeficiency Syndrome / immunology*
T-Lymphocytes, Cytotoxic / immunology
Grant Support
Reg. No./Substance:
0/Epitopes, T-Lymphocyte; 0/Gene Products, env; 0/Gene Products, nef; 0/Histocompatibility Antigens Class I

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