Found 2 matching records:
Displaying record number 53236
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| HXB2 Location |
Tat(36-45)
DNA(5936..5965) |
Tat Epitope Map
|
| Author Location |
Tat(36-45 SUMA) |
| Epitope |
VCFMTKGLGI
|
Epitope Alignment
|
|
|
Show epitope variants
|
| Epitope Name |
Tat VI10 |
| Subtype |
B |
|
Species
(MHC/HLA)
|
human(B*15:01) |
| Immunogen |
HIV-1 infection |
| Patient MHC/HLA |
SUMA: A*11:03, A*24:02, B*14:02, B*15:01, C*08:02, C*12:03 |
| Country |
United States |
| Experimental methods |
CD8 T-cell Elispot - IFNγ, Chromium-release assay |
| Keywords |
dynamics, epitope processing, escape, acute/early infection, kinetics, autologous responses, optimal epitope |
Notes
- Primary CD8+ T-cell response to Env, Tat and Gag and the extent, kinetics and mechanisms of viral escape were examined in three patients. Rapid escape, within weeks from infection, from HIV specific CTL responses was observed in all three patients, but the kinetics and extent of the escape differed depending on the breadth and co-dominant distribution of CTL-mediated pressure. The two patients that rapidly declined had more focused immunodominant responses, while the single patient that had low viral load and stable CD4 counts for seven years had a broad co-dominant response and less escape.
- The patient SUMA maintained low viral loads and stable CD4 T cell counts through seven years of follow up. In contrast to more rapid progressors, WEAU and BORI, SUMA a broad response to 24 epitopes, with little immunodominance. Two peptides were somewhat more intensely recognized in acute infection, but this response leveled out early on.
- Only four epitopes were found to acquire escape mutations in SUMA over time. Early in infection, three overlapping epitopes in Tat carried mutations: FHCQVCFMTK, VCFMTKGLGI, and MTKGLGISY. An M->T substitution was evident during acute infection in the first sample, at four days of the onset of symptoms, and a rare second variant was seen at day 20 that added a K->E substitution. The M->T substitution abrogated responses to FHCQVCFtTK, VCFtTKGLGI, but not in the third epitope tTKGLGISY. By day 69 a double mutation was evident that persisted through day 435, F->L and T->K. Variants lHCQVCFMkK, VCFMkKGLGI were not recognized, and impact processing of the MkKGLGISY epitope.
- Dynamics of this response are shown in Fig. S1 of Yang2019 which developed mathematical models with data from Jones2004. Yang2019 concluded that, in general, relative CTL response breadth increased moderately during the first symptomatic month and then remained relatively stable through the first 400 days post-infection. Analysis also suggested slow expansion kinetics for most HIV-specific CTL responses and the presence of intra- and interclonal competition.
References
Jones2004
Nicola A. Jones, Xiping Wei, Darren R. Flower, MaiLee Wong, Franziska Michor, Michael S. Saag, Beatrice H. Hahn, Martin A. Nowak, George M. Shaw, and Persephone Borrow. Determinants of Human Immunodeficiency Virus Type 1 Escape from the Primary CD8+ Cytotoxic T Lymphocyte Response. J. Exp. Med., 200(10):1243-1256, 15 Nov 2004. PubMed ID: 15545352.
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Yang2019
Yiding Yang, and Vitaly V. Ganusov. Defining Kinetic Properties of HIV-Specific CD8(+) T-Cell Responses in Acute Infection. Microorganisms, 7(3):microorganisms7030069 doi, Mar 2019. PubMed ID: 30836625
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Displaying record number 57438
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Notes
- 3 subjects with acute HIV infection were studied longitudinally by 454-ultra deep-sequencing of 4 HIV-1 epitope regions that have early recognition and escape. Over 50 variant forms of each CTL epitope targeted during the first 3-6 weeks of infection were found, i.e. 7-25 times more than variation in the control V3 region of Env, at earlier times. In very early infection, reversions were seen where immune pressure was considerable but they were absent outside epitopes. A strong case was made for establishment of infection via a single virus.
- All 3 subjects' epitopes have been tested in previous publications.
- In patient SUMA, 3 escape lineages come from transmitted Tat region FY16, FHCQVCFMTKGLGISY, containing this epitope, VI10: lHCQVCFMkKGLGISY; FHCQVCFMkKGLGISY; FHCQdCFMkKGLGISY. The rate of accumulation/loss in FY16 is -0.14.
References
Fischer2010
Will Fischer, Vitaly V. Ganusov, Elena E. Giorgi, Peter T. Hraber, Brandon F. Keele, Thomas Leitner, Cliff S. Han, Cheryl D. Gleasner, Lance Green, Chien-Chi Lo, Ambarish Nag, Timothy C. Wallstrom, Shuyi Wang, Andrew J. McMichael, Barton F. Haynes, Beatrice H. Hahn, Alan S. Perelson, Persephone Borrow, George M. Shaw, Tanmoy Bhattacharya, and Bette T. Korber. Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-Deep Sequencing. PLoS One, 5(8):e12303, 2010. PubMed ID: 20808830.
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