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Displaying record number 54691

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HXB2 Location	Tat(32-41) DNA(5924..5953)	Tat Epitope Map
Author Location	Tat(32-41)
Epitope	FHCQVCFITK	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A*11:03, A*24:02, B*14:02, B*15:01
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	HAART, ART, escape, viral fitness and reversion

Notes

• In order to reconcile apparent conflicts between a CTL-protective role as suggested by HLA-1 alleles associated with different rates of progression to AIDS, and a CTL non-protective role as suggested by the fact that virus clearance following ART is not impaired in advanced AIDS, a model is made that quantifies the efficiency of HIV-1-specific CTLs in vivo. As a surrogate for the actual rate of CTL-killing of infected cells, the model rests on calculating virus escape rate for an epitope and subtracting its reversion rate upon transmission to a non-restricting HLA bearing host. It is shown that CTLs recognizing a single epitope kill only 2% of productively infected CD4+ cells. The rate of CTL lysis was found to be significantly faster during primary infection than in chronic infection. However, the authors suggest that small differences in CTL lysis rate can translate into large differences in terms of absolute numbers of infected cells killed, which are likely to be clinically relevant.
• The best estimate of escape rate for this epitope, FHCQVCFITK, was found to be 0.066 (optimistic escape rate = 0.189) per day, with SE of 0.032.
• In this region of Tat there were 3 overlapping CTL epitopes. A T to K mutation at Tat 32 completely abolished in vitro CTL lysis against all three epitopes. In addition, an M to T mutation at Tat 31 completely abolished recognition of two of the epitopes (third not tested). Quantifying the outgrowth of both of the mutations will overestimate the efficiency of a single CTL response.

References

Asquith2006 Becca Asquith, Charles T. T. Edwards, Marc Lipsitch, and Angela R. McLean. Inefficient Cytotoxic T Lymphocyte-Mediated Killing of HIV-1-Infected Cells In Vivo. PLoS Biol., 4(4):e90, Apr 2006. PubMed ID: 16515366. Show all entries for this paper.