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Displaying record number 54498

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	p17(77-85)
Epitope	SLYNTVATL	Epitope Alignment
		Show epitope variants
Epitope Name	SL9
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, HLA binding
Keywords	subtype comparisons, escape, acute/early infection, variant cross-reactivity, viral fitness and reversion, HLA associated polymorphism

Notes

• The evolution of SLYNTVATL epitope was analyzed over 10 to 20 years in 76 patients and it was found that two opposing selective forces act on the epitope in HLA-A2+ patients. One is caused by an effective CTL pressure, resulting in escape. The main escape mutations were in positions 3, 6 and 8 of the epitope. The other force is selection for optimal viral growth, where the wild-type epitope's index amino acids are selected for. These common evolutionary pathways for the epitope were conserved across several HIV subtypes; while the balance between the opposing evolutionary pathways is suggested to determine variants in a patient at any given time. Fitness cost to SL9 variant generation leading to CTL escape also contributes to lower viral loads in such patients.
• Most variation in this epitope affects TCR recognition as shown by binding studies. Heterogenous CTL responses in patients to viral epitope variants also suggest that the advantage of any single mutation in SL9 is host (and HLA) dependent.
• CTL selection can differ between compartments as seen in compartmentalization of epitope variants between blood and cervix samples.

References

Iversen2006 Astrid K. N. Iversen, Guillaume Stewart-Jones, Gerald H. Learn, Natasha Christie, Christina Sylvester-Hviid, Andrew E. Armitage, Rupert Kaul, Tara Beattie, Jean K. Lee, Yanping Li, Pojchong Chotiyarnwong, Tao Dong, Xiaoning Xu, Mark A. Luscher, Kelly MacDonald, Henrik Ullum, Bente Klarlund-Pedersen, Peter Skinhøj, Lars Fugger, Søren Buus, James I. Mullins, E. Yvonne Jones, P. Anton van der Merwe, and Andrew J. McMichael. Conflicting Selective Forces Affect T Cell Receptor Contacts in an Immunodominant Human Immunodeficiency Virus Epitope. Nat. Immunol., 7(2):179-189, Feb 2006. PubMed ID: 16388312. Show all entries for this paper.