Search CTL/CD8+ T-Cell Epitope Database

Found 7 matching records:

Displaying record number 58377

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HXB2 Location	Gag(481-489) p2p7p1p6(118-126) DNA(2230..2256)	Gag Epitope Map
Author Location	Gag(481-498)
Epitope	`KELYPLASL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	CH040: A02:01, A31:01, B40:01, B44:02, C03:02, C05:01
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	dynamics, escape, acute/early infection, autologous responses, characterizing CD8+ T cells

Notes

Multifunctionality of CTL against transmitted or founder HIV-1 isolates during early or acute infection was examined for correlation with escape mutation selection. The earliest CTL responses were oligofunctional, and progressively became more multifunctional. A significant association was found between total CTL response and order of escape selection, and between epitope entropy with the rate of emergence of escape mutants.
18-mer KELYPLASLRSLFGNDPS (Gag 481-498) contains epitope KELYPLASL, that shows no evidence of escape up to 412 days from onset of symptoms (DFOSx). This epitope elicited CTL response in patient CH40.

References

Ferrari2011 Guido Ferrari, Bette Korber, Nilu Goonetilleke, Michael K. P. Liu, Emma L. Turnbull, Jesus F. Salazar-Gonzalez, Natalie Hawkins, Steve Self, Sydeaka Watson, Michael R. Betts, Cynthia Gay, Kara McGhee, Pierre Pellegrino, Ian Williams, Georgia D. Tomaras, Barton F. Haynes, Clive M. Gray, Persephone Borrow, Mario Roederer, Andrew J. McMichael, and Kent J. Weinhold. Relationship between Functional Profile of HIV-1 Specific CD8 T Cells and Epitope Variability with the Selection of Escape Mutants in Acute HIV-1 Infection. PLoS Pathog., 7(2):e1001273, 2011. PubMed ID: 21347345. Show all entries for this paper.

Displaying record number 60965

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HXB2 Location	Gag(481-489) p2p7p1p6(118-126) DNA(2230..2256)	Gag Epitope Map
Author Location	p6(33-41)
Epitope	`KELYPLASL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*40)
Immunogen	HIV-1 infection
Patient MHC/HLA	98621: A02:01:01G, B40:01:01G, B44:02:01G, C03:04:01G, C05:01; 51729: A24:02, A24:02, B35:05, B40:01, C03:04, C*04:01
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

The extent to which set-point viremia is affected by early HIV-infection T cell responses to either conserved or variable epitopes was studied. 23 ART-naive subjects were characterized for CTL responses for 6 months, postinfection. While most CTL responses (73/123) were targeted against variable HIV-1 epitopes, recognition of conserved epitopes (16/123) was associated with lower set point viremia. This was independent of HLA type and also functional avidity of the CTL response. Most of the conserved responses were targeted to Gag and Pol epitopes.
KELYPLASL, restricted by B*40, was recognized by 2 patients with the restricting allele.

References

Kunwar2013 Pratima Kunwar, Natalie Hawkins, Warren L. Dinges, Yi Liu, Erin E. Gabriel, David A. Swan, Claire E. Stevens, Janine Maenza, Ann C. Collier, James I. Mullins, Tomer Hertz, Xuesong Yu, and Helen Horton. Superior Control of HIV-1 Replication by CD8+ T Cells Targeting Conserved Epitopes: Implications for HIV Vaccine Design. PLoS One, 8(5):e64405, 2013. PubMed ID: 23741326. Show all entries for this paper.

Displaying record number 57383

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HXB2 Location	Gag(481-489) p2p7p1p6(118-126) DNA(2230..2256)	Gag Epitope Map
Author Location	Gag(481-489)
Epitope	`KELYPLASL`	Epitope Alignment
Epitope Name	KL9
Subtype	B
Species (MHC/HLA)	human(B*40)
Immunogen	in vitro stimulation or selection, HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	TCR usage, assay or method development, chronic infection

Notes

By using a modified spectratyping (immunoscoping) method, epitope-specific TCR breadth and sequences were quantitated rapidly. Overall magnitude of HIV-1 specific CTL responses to chronic infection were limited by the clonal breadth of TCR generated against HIV-1 epitopes tested in 12 patients with chronic, untreated infection.
CTL response specific to epitope KL9 was studied, TCR usage was BV04, BV07, BV09 in patient 00016.

References

Balamurugan2010 Arumugam Balamurugan, Hwee L. Ng, and Otto O. Yang. Rapid T Cell Receptor Delineation Reveals Clonal Expansion Limitation of the Magnitude of the HIV-1-Specific CD8+ T Cell Response. J. Immunol., 185(10):5935-5942, 15 Nov 2010. PubMed ID: 20944001. Show all entries for this paper.

Displaying record number 62538

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HXB2 Location	Gag(481-489) p2p7p1p6(118-126) DNA(2230..2256)	Gag Epitope Map
Author Location	Gag(481-489)
Epitope	`KELYPLASL`	Epitope Alignment
Epitope Name	KL9-G
Subtype	B
Species (MHC/HLA)	human(B*40)
Immunogen	HIV-1 infection
Patient MHC/HLA	S00016: A03, A32, B18, B40, C02, C07
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	dynamics, chronic infection

Notes

This report analyzed 29 CTL responses against 23 HIV-1 epitopes in 9 untreated chronically infected "controllers" and identified inverse correlations between epitope variability and CTL clonal stability over time and between epitope variability and CTL clonal breadth.
Over 179 weeks, the KELYPLASL-specific CTL clonal response in individual S00016 demonstrated a 0.39 Sorenson similarity index and a mean breadth of 4.0.
Based on all HIV-1 subtype B sequences in LANL HIV Sequence Database at time of analysis, KELYPLASL had a Simpson diversity index of 0.83.

References

Balamurugan2017 Arumugam Balamurugan, Deon Claiborne, Hwee L. Ng, and Otto O. Yang. HIV-1 Epitope Variability Is Associated with T Cell Receptor Repertoire Instability and Breadth. J. Virol., 91(16), 15 Aug 2017. PubMed ID: 28592539. Show all entries for this paper.

Displaying record number 61511

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HXB2 Location	Gag(481-489) p2p7p1p6(118-126) DNA(2230..2256)	Gag Epitope Map
Author Location	Gag(481-489)
Epitope	`KELYPLASL`	Epitope Alignment
Epitope Name	GagKL9
Subtype	B
Species (MHC/HLA)	human(B*40:02)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	optimal epitope, chronic infection

Notes

CTL controlling HIV-1 and variants were identified from 401 subtype B chronically-infected, treatment-naive Japanese patients. 7 novel epitopes were identified (paper reports 9, correction made via author communication). 9/13 CTL-specific epitopes were conserved among the above subjects and 3/13 were cross-recognized by CTL. 5/13 epitopes were B*5201, 3/13 were B*6701-restricted, both HLA were found to play a predominant role in control of HIV-1. This is the first study to identify HIV-1-specific T cells clinically controlling HIV-1 in a population in whom protective HLA-B*57 and HLA-B*27 are very rare.
Breadth of response of all 13 epitope-specific CTL had synergistic effects on control, directly correlating to CD4 cell count and inversely to plasma viral load (pVL).
HLA-B*4002-restricted GagGM9, KELYPLASL, had 12/393 responding subjects and did not significantly correlate with pVL or CD4 count.

References

Murakoshi2015 Hayato Murakoshi, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, Takuya Naruto, Rie Maruyama, Yoshiko Tamura, Naoki Ishizuka, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi. Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes. J. Virol., 89(10):5330-5339, May 2015. PubMed ID: 25741000. Show all entries for this paper.

Displaying record number 61054

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HXB2 Location	Gag(481-489) p2p7p1p6(118-126) DNA(2230..2256)	Gag Epitope Map
Author Location	p6(33-41)
Epitope	`KELYPLASL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	CH040: A02:01, A31:01, B40:01, B44:02, C03:02, C05:01
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	computational epitope prediction, escape, acute/early infection, mutation acquisition

Notes

17 patients with acute HIV-1 infection were followed to validate that (1) relative escape rate (2) location and identity of escape mutations and (3) epistatic effects on escape, could be predicted within a host by using a simple model based on population genetics and known fitness measures of HIV polyproteins. In general escape location was found most at residues with the lowest fitness cost and escape time correlates with early detection of mutants when T cell response was first detected.
Epitope KELYPLASL had a fitness cost ΔE of 2.388 and T cell response was first detected to it at 16d, escape time was 464.69 days.

References

Barton2016 John P. Barton, Nilu Goonetilleke, Thomas C. Butler, Bruce D. Walker, Andrew J. McMichael, and Arup K. Chakraborty. Relative Rate and Location of Intra-Host HIV Evolution to Evade Cellular Immunity Are Predictable. Nat. Commun., 7:11660, 23 May 2016. PubMed ID: 27212475. Show all entries for this paper.

Displaying record number 58024

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HXB2 Location	Gag(481-489) p2p7p1p6(118-126) DNA(2230..2256)	Gag Epitope Map
Author Location	Gag
Epitope	`KELYPLASL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine-induced immune responses

Vaccine Details

Vaccine type	adenovirus type 5 (Ad5), DNA prime with Ad5 boost
Vaccine strain	B clade IIIB, B clade JRFL, B clade CAM-1
Vaccine component	Gag, Nef, Pol

Notes

T-cell epitope response specificities were examined in uninfected subjects who received the Gag/Pol/Nef vaccine used in the Step trial. Variable epitopes were detected more frequently than would be expected from an unbiased sampling. The most conserved epitopes were detected at a lower frequency, similar to the frequency reported for responses to natural infection, suggesting potential epitope masking. This may be a mechanism used by the virus in both contexts to escape effective T-cell surveillance. Development of vaccine strategies that can elicit a greater breadth, and towards conserved regions of the genome in particular, are critical requirements for effective T-cell based vaccines.
All vacinees had responses to the Gag peptide pool, and most also had responses to the Nef and/or Pol pools. Subsequent mapping using 9mer minipools demonstrated that T-cell epitopes were recognized across the length of all 3 proteins. A total of 105 distinct 9mers were detected, although some of these may have been overlapping 9mers representing a single epitope.
2 vaccinees recognized 9mer KELYPLASL.
Database note: The HLA restriction of this epitope in the LANL database is B40, and both responders were B40-positive.

References

Li2011a Fusheng Li, Adam C. Finnefrock, Sheri A. Dubey, Bette T. M. Korber, James Szinger, Suzanne Cole, M. Juliana McElrath, John W. Shiver, Danilo R. Casimiro, Lawrence Corey, and Steven G Self. Mapping HIV-1 Vaccine Induced T-Cell Responses: Bias Towards Less-Conserved Regions and Potential Impact on Vaccine Efficacy in the Step Study. PLoS One, 6(6):e20479, 2011. PubMed ID: 21695251. Show all entries for this paper.