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.
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 approximately 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 the MHC class I molecule may play an important role in control of immunodeficiency virus replication.
Loffredo
John T
JT
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706, USA.
Sidney
John
J
Bean
Alex T
AT
Beal
Dominic R
DR
Bardet
Wilfried
W
Wahl
Angela
A
Hawkins
Oriana E
OE
Piaskowski
Shari
S
Wilson
Nancy A
NA
Hildebrand
William H
WH
Watkins
David I
DI
Sette
Alessandro
A
D000595:Amino Acid Sequence; D000818:Animals; D004259:DNA-Directed DNA Polymerase; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014779:Virus Replication
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D019151:Peptide Library; D010455:Peptides; C034970:bacteriophage T7 induced DNA polymerase; D004259:DNA-Directed DNA Polymerase