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Displaying record number 53233

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HXB2 Location	Tat(24-32) DNA(5900..5926)	Tat Epitope Map
Author Location	Tat(24-32 WEAU)
Epitope	NCYCKRCCF	Epitope Alignment
		Show epitope variants
Epitope Name	Tat NF9
Subtype	B
Species (MHC/HLA)	human(A*29:02)
Immunogen	HIV-1 infection
Patient MHC/HLA	WEAU: A01, A29, B08, B44
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	dynamics, 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 WEAU had high viral loads and rapid CD4 decline. WEAU mounted 14 detected CTL responses, with distinct patterns of immunodominance. WEAU did not control viral replication well, and escape mutations occurred early and 4/14 had changes that could have resulted in escape, and two were confirmed as escape.
• There was a weak response to this epitope during acute infection that was lost by early infection. The epitope variant kCYCKRCCF was evident by day 72, and other variants were evident in samples taking at 391 and 772 days, including NCYCKkCCF,tCYCKRCCF, kCYCKsCCF and kCYCKkCCF. It was not determined if these were specifically escape mutations, but the CTL response diminished in vivo as kCYCKRCCF variant came up.
• Please see CTL record #53225 for mutations in corresponding autologous variant NCYCKkCCy observed in subtype B-infected patient BORI.
• Dynamics of this response are shown in Fig. S2 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. Show all entries for this paper.

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 Show all entries for this paper.