Search CTL/CD8+ T-Cell Epitope Database

Found 6 matching records:

Displaying record number 60647

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HXB2 Location	Gag(242-250) p24(110-118) DNA(1513..1539)	Gag Epitope Map
Author Location	p24(110-118)
Epitope	TLQEQIGWM	Epitope Alignment
Epitope Name	TM-9
Subtype	B, C
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• Subtype-specific substitutions in two HIV Gag regions (fragments F1, amino acids (aa) 5-46, and F2 aa 100-143) result in novel adaptations that affect epitope processing efficiency. Consequent low epitope abundance is associated with weak T cell response and greater immune escape and therefore with disease state. Conversely, epitopes from these regions when restricted by certain rare HLA I alleles, are associated with greater production and resulting CTL response, therefore delayed disease progression.
• Most epitopes were found to be processed as precursors with N-terminal extensions beyond the optimal epitope. Only 4 epitopes in this region were associated with delayed progression - HLA-B*5701/03-restricted IW9 (ISPRTLNAW), KF11 (KAFSPEVIPMF), TW10 (TSTLQEQIGW) and HLA-B*2705-restricted KK10 (KRWIILGLNK).
• Regardless of ethnic group, white or African, a significant three-way interaction was found between HLA allelic frequency, epitope yield and ethnicity for epitopes of N-terminal fragment F1 (NF1) and C-terminal as well as middle F2 (CF2 and MF2). C-terminal F1 (CF1) epitope yields however, showed a significant difference between ethnic groups. Also, for identical HLA-mediated selection pressure in both Africans and whites, HIV-C had a lower concentration than HIV-B, especially at lower HLA allelic frequencies.
• Epitope TLQEQIGWM, TM-9, is from fragment NF2-MF2, and restricted by HLA-A*02. No subtype B epitope form was studied. For subtype C, the natural processed form was TLQEQIAWM, 0% 4h post-constitutive- and 100% post-immuno-proteasomal processing.

References

Tenzer2014 Stefan Tenzer, Hayley Crawford, Phillip Pymm, Robert Gifford, Vattipally B. Sreenu, Mirjana Weimershaus, Tulio de Oliveira, Anne Burgevin, Jan Gerstoft, Nadja Akkad, Daniel Lunn, Lars Fugger, John Bell, Hansjörg Schild, Peter van Endert, and Astrid K. N. Iversen. HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification. Cell Rep., 7(2):448-463, 24 Apr 2014. PubMed ID: 24726370. Show all entries for this paper.

Displaying record number 52689

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HXB2 Location	Gag(242-250) p24(110-118) DNA(1513..1539)	Gag Epitope Map
Author Location	Gag(242-)
Epitope	TLQEQIGWM	Epitope Alignment
Epitope Name	Gag242
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection, vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay
Keywords	binding affinity, subtype comparisons, computational epitope prediction

Vaccine Details

Notes

• HLA-A2-restricted HIV-1 CTL epitopes were computationally predicted. Binding affinities for HLA-A*0204, immunogenicity in HLA-A*0201 transgenic mice, and responses to the peptides in 17 HIV-1 infected patients were tested. 31 novel conserved A2 epitopes were detected. An average of 4 epitopes were recognized per patient.
• This peptide was an intermediate A2 binder that did not induce CTL and CD8+ T-cell IFN gamma responses in mice. Responses were detected in 2/17 HIV+ HLA-A2 subjects.

References

Corbet2003 Sylvie Corbet, Henrik Vedel Nielsen, Lasse Vinner, Sanne Lauemoller, Dominic Therrien, Sheila Tang, Gitte Kronborg, Lars Mathiesen, Paul Chaplin, Søren Brunak, Søren Buus, and Anders Fomsgaard. Optimization and Immune Recognition of Multiple Novel Conserved HLA-A2, Human Immunodeficiency Virus Type 1-Specific CTL Epitopes. J. Gen. Virol., 84(Pt 9):2409-2421, Sep 2003. PubMed ID: 12917462. Show all entries for this paper.

Displaying record number 55368

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HXB2 Location	Gag(242-250) p24(110-118) DNA(1513..1539)	Gag Epitope Map
Author Location
Epitope	TLQEQIGWM	Epitope Alignment
		Show epitope variants
Epitope Name	Gag 242
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Denmark
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords

Notes

• 11 HLA-A2+ (A*0201, A*0220, A*0234 or A*0236), patients' HIV were sequenced. Of 28 epitopes studied, most were conserved and elicited a subdominant CTL response. 9 epitopes in 7 proteins showed T-cell cross reaction. These epitopes were optimized to induce more immunogenic but cross-reacting responses.
• Epitopes in Gag, Pol, Env, Nef were more conserved than epitopes in shorter proteins Vpu, Vif, Vpr and Rev. Most natural epitopes were untargeted or targeted by 1 or 2 patients.
• Gag 242 TLQEQIGWM was found in 8 patients but only 2 had a CTL immune response to it.

References

Thorn2007 Mette Thorn, Sheila Tang, Dominic Therrien, Henrik Kløverpris, Lasse Vinner, Gitte Kronborg, Jan Gerstoft, Sylvie Corbet, and Anders Fomsgaard. Sequence Conservation of Subdominant HLA-A2-Binding CTL Epitopes in HIV-1 Clinical Isolates and CD8+ T-Lymphocyte Cross-Recognition May Explain the Immune Reaction in Infected Individuals. APMIS, 115(6):757-768, Jun 2007. PubMed ID: 17550385. Show all entries for this paper.

Displaying record number 56057

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HXB2 Location	Gag(242-250) p24(110-118) DNA(1513..1539)	Gag Epitope Map
Author Location	Gag(242-)
Epitope	TLQEQIGWM	Epitope Alignment
		Show epitope variants
Epitope Name	Gag242
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Denmark
Experimental methods	Flow cytometric T-cell cytokine assay
Keywords	rate of progression, escape, acute/early infection

Notes

• Comparative genetic and immunological study was conducted of two subjects - patient DK1 with no viremia for >10 years after transient ART and despite continued sexual contact with patient UG1 (his wife) who was an HIV-1-positive non-controller.
• DK1 and UG1 shared most crossover points of recombination but while DK1 had subtype A1 Env, UG1's Env was subtype D. In the shared subtype A1/D regions, homology between the patients' sequences was 98%.
• Out of 23 conserved HLA-A02 epitopes, HLA-A2+ DK1 produced CTL response and IFN-gamma response only to epitope ILKEPVHGV.
• DK1 produced neutralizing antibody only to homologous isolates. It is suggested that early, transient ART may have resulted in full control of viremia and disease via the very narrow specific CTL response and neutralizing antibody.
• Despite carrying HLA-A2, DK1 did not respond to HLA-A2 Gag epitope TLQEQIGWM, though it did elicit response in a cohort of 11 other HIV-1+ HLA-A2+ patients. A variant of this epitope, sLQEQIGWM, was seen in DK1.

References

Fomsgaard2008 Anders Fomsgaard, Lasse Vinner, Dominic Therrien, Louise B. Jørgensen, Claus Nielsen, Lars Mathiesen, Court Pedersen, and Sylvie Corbet. Full-Length Characterization of A1/D Intersubtype Recombinant Genomes from a Therapy-Induced HIV Type 1 Controller during Acute Infection and His Noncontrolling Partner. AIDS Res. Hum. Retroviruses, 24(3):463-472, Mar 2008. PubMed ID: 18373434. Show all entries for this paper.

Displaying record number 57023

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HXB2 Location	Gag(242-250) p24(110-118) DNA(1513..1539)	Gag Epitope Map
Author Location	Gag
Epitope	TLQEQIGWM	Epitope Alignment
Subtype	CRF01_AE
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Sweden
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, computational epitope prediction, vaccine antigen design

Notes

• From HIV-1 sequences of multiple subtypes, bioinformatic prediction generated 174 CTL epitopes from Gag, Pol, Nef, Env and Tat restricted by HLA supertypes A1, A2, A3, A24, B7, B44 and B58; 10 previously-published A2- and B58-restricted epitopes were also included. Of these 184 epitopes, 113 were recognized experimentally in serum from 31 HIV+ patients.
• While Gag, Pol, Env and Nef were highly immunogenic, only 38% of Tat epitopes elicited a response.
• TLQEQIGWM was a predicted epitope restricted by A2 supertype. 1/31 patient(s) responded to it; the patient was known to carry an allele of A2 supertype. Responding patients were infected with HIV clade(s) CRF01_AE.

References

Perez2008 Carina L. Pérez, Mette V. Larsen, Rasmus Gustafsson, Melissa M. Norström, Ann Atlas, Douglas F. Nixon, Morten Nielsen, Ole Lund, and Annika C. Karlsson. Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes. J. Immunol., 180(7):5092-5100, 1 Apr 2008. PubMed ID: 18354235. Show all entries for this paper.

Displaying record number 58468

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HXB2 Location	Gag(242-250) p24(110-118) DNA(1513..1539)	Gag Epitope Map
Author Location	p24(110-118)
Epitope	TLQEQIGWM	Epitope Alignment
Subtype	A1
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Kenya
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Proliferation
Keywords	assay or method development, characterizing CD8+ T cells

Notes

• 24 longitudinally studied HIV-1 (clades A1 or D)-chronically-infected Kenyan subjects were tested for CTL response to 9-mer overlapping p24 peptides. Epitope mapping was assessed not just by IFN-γ EliSpot assays, but by multiparametric flow cytometry of intracellular cytokine staining for IL-2, tumor necrosis factor (TNF-α), chemokine macrophage inflammatory protein 1β (MIP-1β) and degranulation marker CD107a, as well as by proliferation assays. 50/69 epitope-specific responses detected were IFN-γ negative. Several epitope responses had polyfunctional (33%) and proliferative (19%) components. Long term non progressors (LTNP) had more polyfunctional responses of greater magnitude and proliferation than normal progressors (NP).
• 16 subjects were tested specifically with 126 putative epitopes, 50 of which were confirmed. Clade A1 epitope TLQEQIGWM, corresponds to B consensus of the same sequence, and elicited multifunctional IFN-γ and MIP-1β responses to an NP.

References

Richmond2011 Meika Richmond, Lyle R. McKinnon, Sandra A. Koesters Kiazyk, Charles Wachihi, Makobu Kimani, Joshua Kimani, Francis A. Plummer, and T. Blake Ball. Epitope Mapping of HIV-Specific CD8+ T Cell Responses by Multiple Immunological Readouts Reveals Distinct Specificities Defined by Function. J. Virol., 85(3):1275-1286, Feb 2011. PubMed ID: 21084478. Show all entries for this paper.