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Displaying record number 56297
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| HXB2 Location |
Gag(22-30)
p17(22-30)
DNA(853..879) |
Gag Epitope Map
|
| Author Location |
p17(22-30 SF2, HXBc2/Bal R5) |
| Epitope |
RPGGKKKKYK
|
Epitope Alignment
|
|
|
Show epitope variants
|
| Subtype |
B |
|
Species
(MHC/HLA)
|
human(B7) |
| Immunogen |
HIV-1 infection |
| Patient MHC/HLA |
A2, A3, B15, B7, Cw3, Cw6; A29, A3, B44, B7, Cw3, Cw7; A24, A3, B7, B8, Cw7 |
| Country |
United States |
| Experimental methods |
Cytokine production, Degranulation, CD107a and b cell surface mobilization, Flow cytometric T-cell cytokine assay |
| Keywords |
supervised treatment interruptions (STI), immunodominance, variant cross-reactivity, characterizing CD8+ T cells, drug resistance |
Notes
- A detailed analysis of 6 chronically infected patients' CTL responses to autologous virus was performed after ART and SIT (structured interruption of therapy). Qualitative responses including degranulation and production of IFN-gamma, MIP-1beta, TNF-alpha, IL-2, but not memory CD27, CD45RO and CD57 T cells correlated with extended low plasma viremia. Frequency and breadth of CTL response as well as immune escape did not influence virological outcome.
- One patient exhibited drug resistance mutations K170R (to NNRTI efavirenz) and D76N, K70R (to NRTIs).
- Autologous epitopes were preferentially recognized over optimal, consensus sequences.
- Patients with favorable virological outcomes demonstrated CTL recognition within multiple, conserved regions of Gag and Nef.
- Patients with poor virological outcomes recognized optimal epitopes with much lower frequencies, though this was not significant.
- HLA-B7-restricted epitope, RPGGKKKKYK, elicited a response in 3 patients and is found in Gag immunodominant regions WEKIRLRPGGKKKYKL, WEKIRLRPGGKKKYK or LDRWEKIRLRPGGKKKYKL. The autologous sequence in one patient was RPGGKKKrYK and in the other 2 was RPGGKKKKYr.
- In a patient who had one of the lowest viremias, the highest frequency of CTL response was to 2 immunodominant regions in Gag containing epitopes KK9 (KIRLRPGGK), RK9 (RLRPGGKKK) and this epitope p17 RPGGKKKYK.
References
Daucher2008
Marybeth Daucher, David A. Price, Jason M. Brenchley, Laurie Lamoreaux, Julia A. Metcalf, Catherine Rehm, Elizabeth Nies-Kraske, Elizabeth Urban, Christian Yoder, Diane Rock, Julie Gumkowski, Michael R. Betts, Mark R. Dybul, and Daniel C. Douek. Virological Outcome after Structured Interruption of Antiretroviral Therapy for Human Immunodeficiency Virus Infection Is Associated with the Functional Profile of Virus-Specific CD8+ T Cells. J. Virol., 82(8):4102-4114, Apr 2008. PubMed ID: 18234797.
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