Ex vivo SIV-specific CD8 T cell responses in heterozygous animals are primarily directed against peptides presented by a single MHC haplotype

Justin M. Greene, Emily N. Chin, Melisa L. Budde, Jennifer J. Lhost, Paul J. Hines, Benjamin Burwitz, Karl W. Broman, Jennifer E. Nelson, Thomas C. Friedrich, David H. O'Connor

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The presence of certain MHC class I alleles is correlated with remarkable control of HIV and SIV, indicating that specific CD8 T cell responses can effectively reduce viral replication. It remains unclear whether epitopic breadth is an important feature of this control. Previous studies have suggested that individuals heterozygous at the MHC class I loci survive longer and/or progress more slowly than those who are homozygous at these loci, perhaps due to increased breadth of the CD8 T cell response. We used Mauritian cynomolgus macaques with defined MHC haplotypes and viral inhibition assays to directly compare CD8 T cell efficacy in MHC-heterozygous and homozygous individuals. Surprisingly, we found that cells from heterozygotes suppress viral replication most effectively on target cells from animals homozygous for only one of two potential haplotypes. The same heterozygous effector cells did not effectively inhibit viral replication as effectively on the target cells homozygous for the other haplotype. These results indicate that the greater potential breadth of CD8 T cell responses present in heterozygous animals does not necessarily lead to greater antiviral efficacy and suggest that SIV-specific CD8 T cell responses in heterozygous animals have a skewed focus toward epitopes restricted by a single haplotype.

Original languageEnglish (US)
Article numbere43690
JournalPLoS One
Volume7
Issue number8
DOIs
StatePublished - Aug 22 2012
Externally publishedYes

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T-cells
Haplotypes
haplotypes
Animals
T-lymphocytes
peptides
T-Lymphocytes
virus replication
Peptides
animals
cells
loci
Macaca fascicularis
Macaca
Heterozygote
epitopes
Antiviral Agents
Epitopes
Assays
heterozygosity

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ex vivo SIV-specific CD8 T cell responses in heterozygous animals are primarily directed against peptides presented by a single MHC haplotype. / Greene, Justin M.; Chin, Emily N.; Budde, Melisa L.; Lhost, Jennifer J.; Hines, Paul J.; Burwitz, Benjamin; Broman, Karl W.; Nelson, Jennifer E.; Friedrich, Thomas C.; O'Connor, David H.

In: PLoS One, Vol. 7, No. 8, e43690, 22.08.2012.

Research output: Contribution to journalArticle

Greene, JM, Chin, EN, Budde, ML, Lhost, JJ, Hines, PJ, Burwitz, B, Broman, KW, Nelson, JE, Friedrich, TC & O'Connor, DH 2012, 'Ex vivo SIV-specific CD8 T cell responses in heterozygous animals are primarily directed against peptides presented by a single MHC haplotype', PLoS One, vol. 7, no. 8, e43690. https://doi.org/10.1371/journal.pone.0043690
Greene, Justin M. ; Chin, Emily N. ; Budde, Melisa L. ; Lhost, Jennifer J. ; Hines, Paul J. ; Burwitz, Benjamin ; Broman, Karl W. ; Nelson, Jennifer E. ; Friedrich, Thomas C. ; O'Connor, David H. / Ex vivo SIV-specific CD8 T cell responses in heterozygous animals are primarily directed against peptides presented by a single MHC haplotype. In: PLoS One. 2012 ; Vol. 7, No. 8.
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