Found 2 matching records:
Displaying record number 57553
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Notes
- The study analyzed the kinetics of the HIV-specific CD8+ T-cell response in 21 acutely infected subjects. The first responses peaked at as early as 5 days, but were of limited epitope breadth. Responses of additional specificities expanded in subsequent waves, resulting in successive shifts in epitope immunodominance over time. The results document the preferential expansion of CD8+ T cells recognizing a subset of epitopes in acute infection and suggest that the initial T-cell response may influence the efficiency of viral containment in early infection.
- Responses to MTKGLGISY during acute/early infection were compared by IFN-γ ELISPOT and by tetramer immunolabeling. The magnitude of response was lower with ELISPOT. The kinetics was also different, with the peak of responses shifted with ELISPOT compared to tetramer immunolabeling.
References
Turnbull2009
Emma L. Turnbull, MaiLee Wong, Shuyi Wang, Xiping Wei, Nicola A. Jones, Karen E. Conrod, Diana Aldam, Jo Turner, Pierre Pellegrino, Brandon F. Keele, Ian Williams, George M. Shaw, and Persephone Borrow. Kinetics of Expansion of Epitope-Specific T Cell Responses During primary HIV-1 Infection. J. Immunol., 182(11):7131-7145, 1 Jun 2009. PubMed ID: 19454710.
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Displaying record number 53237
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| HXB2 Location |
Tat(39-47)
DNA(5945..5971) |
Tat Epitope Map
|
| Author Location |
Tat(39-47 SUMA) |
| Epitope |
MTKGLGISY
|
Epitope Alignment
|
|
|
Show epitope variants
|
| Epitope Name |
Tat MY9 |
| 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, immunodominance, 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, but the CTL response was strong to MkKGLGISY. The authors provide evidence that the F->L and T->K substitutions impact processing of the MTKGLGISY epitope, as the mutations don't abrogate a CTL response to the peptide, but Tat expressed in target cells doesn't allow recognition of the Tat variant.
- MTKGLGISY was the highest level response in acute and early infection.
- 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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