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Displaying record number 59484

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HXB2 Location	Nef(11-19) DNA(8827..8853)	Nef Epitope Map
Author Location	Nef( pNL4-3)
Epitope	IGWPAVRER	Epitope Alignment
Epitope Name	IR9
Subtype	B
Species (MHC/HLA)	human(A*11:01)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, TCR binding
Keywords	assay or method development, novel epitope

Notes

• Deep Ligand Sequencing (DLS) was used to identify 37 novel HLA-A*1101-restricted epitopes, and 5 previously published ones. HLA-A*1101-expressing CD4⁺ T cells were infected with HIV strain pNL4-3; soluble HLA-A*1101-ligand was recovered and purified, and then ligands (i.e. epitopes) were acid-released. A combination of chromatography and mass spectrometry used to separate the distinct peptides. For each epitope, the HLA binding affinity and median EliSpot response in 23 A*1101-positive patients were determined. This is the first report of direct elution of HIV-1 genome-encoded epitopes.
• Gag and N-terminal Nef epitopes dominate the antigenic profile of epitopes over other HIV-1 proteins (Pol, Env, Vpu). Nef and Pol epitopes, however, were widely recognized. Immunologically reactive epitopes are often atypical in length, particularly in epitope hotspots of Gag and Nef. Epitopes discovered were primarily a result of de novo protein synthesis in the host cell instead of secretory pathway peptide processing.
• IGWPAVRER, IR9 had low TCR binding and was recognized by 3/23 A*1101-positive patients with a median magnitude of 136 SFU/10⁶ PBMC.

References

Yaciuk2014 Jane C. Yaciuk, Matthew Skaley, Wilfried Bardet, Fredda Schafer, Danijela Mojsilovic, Steven Cate, Christopher J. Stewart, Curtis McMurtrey, Kenneth W. Jackson, Rico Buchli, Alex Olvera, Samandhy Cedeño, Montserrat Plana, Beatriz Mothe, Christian Brander, John T. West, and William H. Hildebrand. Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells. J. Virol., 88(22):12992-13004, Nov 2014. PubMed ID: 25165114. Show all entries for this paper.