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

John T. Loffredo, John Sidney, Alex T. Bean, Dominic R. Beal, Wilfried Bardet, Angela Wahl, Oriana E. Hawkins, Shari Piaskowski, Nancy A. Wilson, William H. Hildebrand, David Watkins, Alessandro Sette

Research output: Contribution to journalArticle

77 Citations (Scopus)

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 languageEnglish
Pages (from-to)7763-7775
Number of pages13
JournalJournal of Immunology
Volume182
Issue number12
DOIs
StatePublished - Jun 15 2009
Externally publishedYes

Fingerprint

Virus Replication
Peptides
Epitopes
Macaca mulatta
HIV
T-Lymphocytes
HLA-B27 Antigen
Viremia
Viral RNA
Macaca
HLA-B*27:05 antigen

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 journalArticle

Loffredo, JT, Sidney, J, Bean, AT, Beal, DR, Bardet, W, Wahl, A, Hawkins, OE, Piaskowski, S, Wilson, NA, Hildebrand, WH, Watkins, D & Sette, A 2009, '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', Journal of Immunology, vol. 182, no. 12, pp. 7763-7775. https://doi.org/10.4049/jimmunol.0900111
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. / 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. In: Journal of Immunology. 2009 ; Vol. 182, No. 12. pp. 7763-7775.
@article{0abc31a14034493880ffd96c6a784b7e,
title = "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",
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.",
author = "Loffredo, {John T.} and John Sidney and Bean, {Alex T.} and Beal, {Dominic R.} and Wilfried Bardet and Angela Wahl and Hawkins, {Oriana E.} and Shari Piaskowski and Wilson, {Nancy A.} and Hildebrand, {William H.} and David Watkins and Alessandro Sette",
year = "2009",
month = "6",
day = "15",
doi = "10.4049/jimmunol.0900111",
language = "English",
volume = "182",
pages = "7763--7775",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "12",

}

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 -