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Found 3 matching records:

Displaying record number 53246

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HXB2 Location	Gag(295-303) p24(163-171) DNA(1672..1698)	Gag Epitope Map
Author Location	Gag(295-303 SUMA)
Epitope	`DYVDRFYKT`	Epitope Alignment
Epitope Name	Gag DT9
Subtype	B
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Patient MHC/HLA	SUMA: A11:03, A24:02, B14:02, B15:01, C08:02, C12:03
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	dynamics, acute/early infection, 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, and this was one of the 20 that remained invariant. A low level response was detected at acute infection that persisted through 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.
Patient SUMA autologous epitope DYVDRFYKT overlaps with patient BORI autologous epitope DRFYKTLRAEQ (as published in Jones2004 but Yang2019 published this epitope as DRFYKTLRA).

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.

Displaying record number 60685

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HXB2 Location	Gag(295-303) p24(163-171) DNA(1672..1698)	Gag Epitope Map
Author Location	p24(295-303)
Epitope	`DYVDRFYKT`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Patient MHC/HLA	S2: ; S3: ; S8:
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	dendritic cells, assay or method development, memory cells

Notes

In general, mature IL-12p70-producing dendritic cells (DC) that are responsive to CD40L and loaded with inactive autologous HIV-1 were found to prime naive CTL to respond to a far broader range of conserved and variable Gag peptides than DC-stimulated memory T cells could. Stimulated memory CTL also had lower anti-CD4 T-cell cytolytic function than primed naive CTL. A novel in vitro model of DC immunotherapy was established.
Subject S2 reacted to autologous Gag epitope DYVDRFYKT, part of peptides PKEPFRDYVDRFYKTLRA and FRDYVDRFYKTLRAEQAS which elicited responses of 784 and 359 SFC/10⁶ cells from DC-primed naive T cells versus 0 from primed memory cells. Subject S8, for whom the same peptide was used, elicited 2514 and 2334 for naive T versus 1089 and 0 SFC/10⁶ cells for memory T cells. Peptides used for S3 were different, KQGPKEFRDYVDRFYKTL, KEFRDYVDRFYKTLRAEQ and DYVDRFYKTLRAEQASQE, all of which elicited stronger CTL responses from naive T cells than memory T cells.
This epitope is a variant of previously determined epitopes, YVDRFfKTL and YVDRFfKaL.

References

Smith2016 Kellie N. Smith, Robbie B. Mailliard, Paolo A. Piazza, Will Fischer, Bette T. Korber, Ronald J. Fecek, Deena Ratner, Phalguni Gupta, James I. Mullins, and Charles R. Rinaldo. Effective Cytotoxic T Lymphocyte Targeting of Persistent HIV-1 during Antiretroviral Therapy Requires Priming of Naive CD8+ T Cells. MBio, 7(3), 31 May 2016. PubMed ID: 27247230. Show all entries for this paper.

Displaying record number 61781

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HXB2 Location	Gag(295-303) p24(163-171) DNA(1672..1698)	Gag Epitope Map
Author Location
Epitope	`DYVDRFYKT`	Epitope Alignment
Epitope Name	DT9
Subtype	B
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection, vaccine
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Intracellular cytokine staining
Keywords	vaccine-induced immune responses, variant cross-reactivity

Notes

Specific T cells - from 120 ART-naive, infected Japanese subjects previously exposed to the tHIVconsvX vaccine - that have the ability to suppress HIV-1 replication were identified as recognizing 17 optimal Gag epitopes. 9/17 eptiopes were associated with lower pVL and higher CD4 count, of which 5 remain associated with positive clinical outcome in 221 HIV-1 infected subjects and cross-recognized major HIV-1 variants. 2/5 epitopes were novel. Candidate tHIVconsvX vaccine is composed of 6 conserved Gag and Pol regions.
A*2402-restricted epitope DYVDRFYKT was found in 15-mer peptide pairs C078/079 and C080/081. 9 HLA-carrying and 7 non-HLA-A*2402-carrying responders to this epitope were detected by EliSpot out of 50 subjects.

References

Murakoshi2018 Hayato Murakoshi, Chengcheng Zou, Nozomi Kuse, Tomohiro Akahoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, Tomáš Hanke, and Masafumi Takiguchi. CD8+ T Cells Specific for Conserved, Cross-Reactive Gag Epitopes with Strong Ability to Suppress HIV-1 Replication. Retrovirology, 15(1):46, 3 Jul 2018. PubMed ID: 29970102. Show all entries for this paper.