Search CTL/CD8+ T-Cell Epitope Database

Found 22 matching records:

Displaying record number 54672

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HXB2 Location	Gag(18-26) p17(18-26) DNA(841..867)	Gag Epitope Map
Author Location	p17(18-26)
Epitope	`KIRLRPGGK`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A01:01, A03:01, B08:01; A02:01, A31:01, B35:01, B*39:05
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 escape rate for this epitope, KIRLRPGGK, was 0.002 (SE 0.006), and best estimate reversion rate was 0/day with a SE of 0.
The variant K26R confers escape in A*0301+ individuals. On transmission to an HLA A*0301-negative recipient, the mutation did not revert to wild type over a period of 1 year.

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.

Displaying record number 54678

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HXB2 Location	Gag(20-28) p17(20-28) DNA(847..873)	Gag Epitope Map
Author Location	p17(20-28)
Epitope	`RLRPGGKKK`	Epitope Alignment
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A01:01, A03:01, B*08:01
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, RLRPGGKKK, was found to be 0.032/day, with SE of 0.008.
The K28T substitution conferred escape from CTL responses of both the RLRPGGKKK and GGKKKYRL epitopes.

References

Displaying record number 54681

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HXB2 Location	Gag(21-35) p17(21-35) DNA(850..894)	Gag Epitope Map
Author Location	p17(21-35)
Epitope	`LRPGGKKKYKLKHIV`	Epitope Alignment
Species (MHC/HLA)	human(B8)
Immunogen	HIV-1 infection
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, LRPGGKKKYKLKHIV, was found to be -0.001/day (upper bound on rate of escape = 0.085), with SE of 0.003.
In the subject studied, K26R grew out steadily to 95% frequency, but then there was a progressive re-emergence of the wild type. If data from all time points were fitted, then the mutant actually had a negative growth rate because it was eventually out-competed by the wild type.

References

Displaying record number 54679

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HXB2 Location	Gag(24-31) p17(24-31) DNA(859..882)	Gag Epitope Map
Author Location	p17(24-31)
Epitope	`GGKKKYRL`	Epitope Alignment
Species (MHC/HLA)	human(B*08:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A01:01, A03:01, B*08:01
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, GGKKKYRL, was found to be 0.032/day, with SE of 0.008.
The K28T substitution conferred escape from CTL responses of both the RLRPGGKKK and GGKKKYRL epitopes.

References

Displaying record number 54675

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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
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
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, SLYNTVATL, was found to be 0.006/day (upper bound on rate of escape = 0.008), with SE of 0.001.
Four variants were shown to confer escape (Y79F, Y79F-V82I, Y79F-T84V, V82I-T84V), and variant A83V was also present but untested for CTL response.

References

Displaying record number 54689

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HXB2 Location	Gag(119-127) p17(119-127) DNA(1144..1170)	Gag Epitope Map
Author Location	p17(119-127)
Epitope	`AADTGNSSQ`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A29:02, B14:02
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, AADTGNSSQ, was found to be 0.119/day, with SE of 0.021.
A number of mutations in this epitope (Gag AQ9) abolished recognition completely. Gag AQ9 overlapped with a second epitope (Gag NP10), and a number of mutations conferring escape from the AQ9 directed response were shown to confer escape from NP10 responses as well. This will lead to an overestimate of the importance of a single CTL response. Escape at NP10 was not quantified separately on the grounds that it was insufficiently independent from escape at AQ9.

References

Displaying record number 54670

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HXB2 Location	Gag(147-155) p24(15-23) DNA(1228..1254)	Gag Epitope Map
Author Location	p24(15-23)
Epitope	`ISPRTLNAW`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
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 reversion rate for this epitope, ISPRTLNAW, was found to be -0.005/day with a SE of 0.
An A14P substitution in the flanking region of this B57-restricted epitope prevented correct processing of the epitope and conferred CTL escape. On transfer of this variant to an HLA-B57- individual, the frequency of the escape mutant actually increased giving a negative reversion rate of -0.005/day. This is consistent with in vitro replication and competition assays as well as with the accumulation of this mutation in the population, suggesting that A14P does not carry a fitness cost.

References

Displaying record number 54671

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HXB2 Location	Gag(240-249) p24(108-117) DNA(1507..1536)	Gag Epitope Map
Author Location	p24(108-117)
Epitope	`TSTLQEQIGW`	Epitope Alignment
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
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 reversion rates for this epitope, TSTLQEQIGW, in 3 different subjects were found to be 0.016, 0, and 0.005/day with SEs of 0.007, 0, and 0.001 respectively.
Gag p24 T110N confers escape in subjects expressing HLA-B57 and HLA-B5801. On transmission from an HLA-B57+ donor to an B57/B5801- recipient, the mutation rapidly reverted to wild type (a=0.016/day). Gag p24 G116A confers escape in subjects expressing B57 and B5801. On transmission from an HLA-B57+ donor to an B57/B5801- recipient, the mutation did not revert to wild type over the 8-year observation period, suggesting that the mutation was neutral (a=0/day). The escape variant in Gag p24 T110N was studied in a further HLA-B57+ to HLA-B57/B5801- transmission pair where it reverted to wild type (a=0.005/day).

References

Displaying record number 54674

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HXB2 Location	Gag(263-272) p24(131-140) DNA(1576..1605)	Gag Epitope Map
Author Location	p24(131-140)
Epitope	`KRWIIMGLNK`	Epitope Alignment
Species (MHC/HLA)	human(B27)
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A3, B27:05, B35; A2, A22, B27:05, B35
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 rates for this epitope, KRWIIMGLNK, were found in 3 subjects to be 0.002, 0.001 and 0.010/day, with SEs of 0.003, 0.003 and 0.011 respectively.
The escape mutation was R132K in all cases.

References

Displaying record number 54686

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HXB2 Location	Pol(283-290) RT(128-135) DNA(2931..2954)	Pol Epitope Map
Author Location	RT Pol(128-135)
Epitope	`TAFTIPSI`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, A32, B15, B51
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, YFPDWQDYT, was found to be 0.002/day (optimistic escape rate = 0.012), with SE of 0.001.
In the subject studied, the monotonic outgrowth of a I290T mutation in Pol was observed over a period of 817 days.

References

Displaying record number 54690

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HXB2 Location	Tat(24-32) DNA(5900..5926)	Tat Epitope Map
Author Location	Tat(24-32)
Epitope	`NCYCKKCCF`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A29:02, B14:02; A29:02, B08:01, B*44:03
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 rates for this epitope, NCYCKKCCF, were found to be 0.047 and 0.006/day (optimistic escape rates = 0.051 and 0.013), with SE of 0.054 and 0.004 respectively.
In the first subject, 3 mutations in this Tat epitope (N24K, N24K+K29R, N24K+K29Q) were all shown to confer escape. In the second subject, peptide recognition was not tested, but by analogy with another patient it was suggested that a N to K mutation at position 1 of the epitope Tat 24-32 conferred escape. An additional N to T mutation at position 1 was also considered likely to be an escape mutation.

References

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	A11:03, A24:02, B14:02, B15:01
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

Displaying record number 54692

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HXB2 Location	Tat(36-45) DNA(5936..5965)	Tat Epitope Map
Author Location	Tat(36-45)
Epitope	`VCFITKALGI`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A11:03, A24:02, B14:02, B15:01
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, VCFITKALGI, 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

Displaying record number 54693

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HXB2 Location	Tat(39-47) DNA(5945..5971)	Tat Epitope Map
Author Location	Tat(39-47)
Epitope	`ITKALGISY`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A11:03, A24:02, B14:02, B15:01
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, VCFITKALGI, 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

Displaying record number 54677

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp160(31-39)
Epitope	`AENLWVTVY`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A29, B44, B8
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, AENLWVTVY, was found to be 0.048/day (upper bound on rate of escape = 0.053), with SE of 0.022.
Mutations at position 30 (E30G and E30A) were shown to confer escape.

References

Displaying record number 54688

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HXB2 Location	gp160(73-81) gp120(73-81) DNA(6441..6467)	gp160 Epitope Map
Author Location	gp41(73-81)
Epitope	`ACVPTDPNP`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A29:02, B14:02
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, ACVPTDPNP, was found to be 0.023/day, with SE of 0.016.
Five mutations at the fifth position of Env gp41 73-81 were all shown to confer limited CTL escape.

References

Displaying record number 54683

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HXB2 Location	gp160(190-208) gp120(190-208) DNA(6792..6848)	gp160 Epitope Map
Author Location	gp41(190-208)
Epitope	`SYKLTSCNTSVITQACPKV`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, A32, B15, B51
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, SYKLTSCNTSVITQACPKV, was found to be 0.005/day, with SE of 0.001.
In the subject studied, the monotonic outgrowth of a Q199K mutation in Env gp41 was observed over a period of 1,028 days.

References

Displaying record number 54687

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HXB2 Location	gp160(209-217) gp120(209-217) DNA(6849..6875)	gp160 Epitope Map
Author Location	gp160(209-217)
Epitope	`SFEPIPIHY`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A29:02, B14:02; A29:02, B08:01, B*44:03
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 estimates of escape rate for this epitope, SFEPIPIHY, were found to be 0.072 and 0.041/day (optimistic escape rate = 0.13), with SEs of 0.041 and 0.005 respectively, in 2 subjects.
In the first subject, rapid loss of wild type at this epitope (primarily due to a E211D mutation) was observed. In the second subject, a Y217F mutation grew out over time.

References

Displaying record number 54680

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRRMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Patient MHC/HLA	A01:01, A03:01, B*08:01
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 estimates of escape rate for this epitope, QVPLRRMTYK, were found to be 0.022 and 0.003/day (upper bound on rate of escape = 0.05 and 0.011), with SEs of 0.013 and 0.003 respectively, in 2 subjects.
In the first subject, a number of mutations arose in Nef 73-82; all but one of these (V74A) elicited a very weak ELISpot response compared to the wild type. In the second subject, large epitope deletions and a V74I substitution in the recognized epitope were selected for.

References

Displaying record number 54684

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HXB2 Location	Nef(90-97) DNA(9064..9087)	Nef Epitope Map
Author Location	Nef(90-97)
Epitope	`FLKEKGGL`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, B7, B8
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, FLKEKGGL, was found to be 0.049/day, with SE of 0.012.
In the subject studied, a number of variants arose in the Nef epitope 90-97 (including complete epitope deletion) that were poorly recognized by CTL or escaped recognition completely.

References

Displaying record number 54685

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HXB2 Location	Nef(120-128) DNA(9154..9180)	Nef Epitope Map
Author Location	Nef(120-128)
Epitope	`YFPDWQDYT`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, A32, B15, B51
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, YFPDWQDYT, was found to be 0.002/day (optimistic escape rate = 0.012), with SE of 0.001.
In the subject studied, the fluctuating outgrowth of a Q125D mutation in Nef was observed over a period of 1,361 days.

References

Displaying record number 54673

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HXB2 Location	Nef(134-143) DNA(9196..9225)	Nef Epitope Map
Author Location	Nef(134-143)
Epitope	`RYPLTFGWCY`	Epitope Alignment
Species (MHC/HLA)	human(A24)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A26, B51, B62; A2, B39, B60
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 estimates of reversion rates for this epitope, RYPLTFGWCY/F, in 2 subjects were found to be -0.014 and 0.005/day with SEs of 0.
A Y135F substitution was shown to confer escape from an A24-restricted response by prevention of epitope processing. In an HLA A24- individual, the mutation rapidly reverted to wild type. Reversion of the Y135F escape mutant was observed in a second A24- individual. The model fitted the data well, giving a rate of 0.005/day. In this subject, the 135F-138C variant was out-competed by a 135Y-138C variant rather than by the wild type (135Y-138T). The rate of reversion with respect to the wild type is zero.