Abstract
HLA-B27- and -B57-positive HIV-infected humans have long been associated with control of HIV replication, implying that CD8+ T cell responses contribute to control of viral replication. In a similar fashion, 50% of Mamu-B*08-positive Indian rhesus macaques control SIVmac239 replication and become elite controllers with chronic-phase viremia <1000 viral RNA copies/ml. Interestingly, Mamu-B*08-restricted SIV-derived epitopes appeared to match the peptide binding profile for HLA-B*2705 in humans. We therefore defined a detailed peptide-binding motif for Mamu-B*08 and investigated binding similarities between the macaque and human MHC class I molecules. Analysis of a panel of ∼900 peptides revealed that despite substantial sequence differences between Mamu-B*08 and HLA-B*2705, the peptide-binding repertoires of these two MHC class I molecules share a remarkable degree of overlap. Detailed knowledge of the Mamu-B*08 peptide-binding motif enabled us to identify six additional novel Mamu-B*08-restricted SIV-specific CD8+ T cell immune responses directed against epitopes in Gag, Vpr, and Env. All 13 Mamu-B*08- restricted epitopes contain an R at the position 2 primary anchor and 10 also possess either R or K at the N terminus. Such dibasic peptides are less prone to cellular degradation. This work highlights the relevance of the Mamu-B*08-positive SIV-infected Indian rhesus macaque as a model to examine elite control of immunodeficiency virus replication. The remarkable similarity of the peptide-binding motifs and repertoires for Mamu-B*08 and HLA-B*2705 suggests that the nature of the peptide bound by theMHCclass I molecule may play an important role in control of immunodeficiency virus replication.
| Original language | English |
|---|---|
| Pages (from-to) | 7763-7775 |
| Number of pages | 13 |
| Journal | Journal of Immunology |
| Volume | 182 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 15 2009 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Medicine(all)
Cite this
Two MHC class I molecules associated with elite control of immunodeficiency virus replication, Mamu-B*08 and HLA-B*2705, bind peptides with sequence similarity. / Loffredo, John T.; Sidney, John; Bean, Alex T.; Beal, Dominic R.; Bardet, Wilfried; Wahl, Angela; Hawkins, Oriana E.; Piaskowski, Shari; Wilson, Nancy A.; Hildebrand, William H.; Watkins, David; Sette, Alessandro.
In: Journal of Immunology, Vol. 182, No. 12, 15.06.2009, p. 7763-7775.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Two MHC class I molecules associated with elite control of immunodeficiency virus replication, Mamu-B*08 and HLA-B*2705, bind peptides with sequence similarity
AU - Loffredo, John T.
AU - Sidney, John
AU - Bean, Alex T.
AU - Beal, Dominic R.
AU - Bardet, Wilfried
AU - Wahl, Angela
AU - Hawkins, Oriana E.
AU - Piaskowski, Shari
AU - Wilson, Nancy A.
AU - Hildebrand, William H.
AU - Watkins, David
AU - Sette, Alessandro
PY - 2009/6/15
Y1 - 2009/6/15
N2 - HLA-B27- and -B57-positive HIV-infected humans have long been associated with control of HIV replication, implying that CD8+ T cell responses contribute to control of viral replication. In a similar fashion, 50% of Mamu-B*08-positive Indian rhesus macaques control SIVmac239 replication and become elite controllers with chronic-phase viremia <1000 viral RNA copies/ml. Interestingly, Mamu-B*08-restricted SIV-derived epitopes appeared to match the peptide binding profile for HLA-B*2705 in humans. We therefore defined a detailed peptide-binding motif for Mamu-B*08 and investigated binding similarities between the macaque and human MHC class I molecules. Analysis of a panel of ∼900 peptides revealed that despite substantial sequence differences between Mamu-B*08 and HLA-B*2705, the peptide-binding repertoires of these two MHC class I molecules share a remarkable degree of overlap. Detailed knowledge of the Mamu-B*08 peptide-binding motif enabled us to identify six additional novel Mamu-B*08-restricted SIV-specific CD8+ T cell immune responses directed against epitopes in Gag, Vpr, and Env. All 13 Mamu-B*08- restricted epitopes contain an R at the position 2 primary anchor and 10 also possess either R or K at the N terminus. Such dibasic peptides are less prone to cellular degradation. This work highlights the relevance of the Mamu-B*08-positive SIV-infected Indian rhesus macaque as a model to examine elite control of immunodeficiency virus replication. The remarkable similarity of the peptide-binding motifs and repertoires for Mamu-B*08 and HLA-B*2705 suggests that the nature of the peptide bound by theMHCclass I molecule may play an important role in control of immunodeficiency virus replication.
AB - HLA-B27- and -B57-positive HIV-infected humans have long been associated with control of HIV replication, implying that CD8+ T cell responses contribute to control of viral replication. In a similar fashion, 50% of Mamu-B*08-positive Indian rhesus macaques control SIVmac239 replication and become elite controllers with chronic-phase viremia <1000 viral RNA copies/ml. Interestingly, Mamu-B*08-restricted SIV-derived epitopes appeared to match the peptide binding profile for HLA-B*2705 in humans. We therefore defined a detailed peptide-binding motif for Mamu-B*08 and investigated binding similarities between the macaque and human MHC class I molecules. Analysis of a panel of ∼900 peptides revealed that despite substantial sequence differences between Mamu-B*08 and HLA-B*2705, the peptide-binding repertoires of these two MHC class I molecules share a remarkable degree of overlap. Detailed knowledge of the Mamu-B*08 peptide-binding motif enabled us to identify six additional novel Mamu-B*08-restricted SIV-specific CD8+ T cell immune responses directed against epitopes in Gag, Vpr, and Env. All 13 Mamu-B*08- restricted epitopes contain an R at the position 2 primary anchor and 10 also possess either R or K at the N terminus. Such dibasic peptides are less prone to cellular degradation. This work highlights the relevance of the Mamu-B*08-positive SIV-infected Indian rhesus macaque as a model to examine elite control of immunodeficiency virus replication. The remarkable similarity of the peptide-binding motifs and repertoires for Mamu-B*08 and HLA-B*2705 suggests that the nature of the peptide bound by theMHCclass I molecule may play an important role in control of immunodeficiency virus replication.
UR - http://www.scopus.com/inward/record.url?scp=67649172577&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67649172577&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0900111
DO - 10.4049/jimmunol.0900111
M3 - Article
C2 - 19494300
AN - SCOPUS:67649172577
VL - 182
SP - 7763
EP - 7775
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -