Search CTL/CD8+ T-Cell Epitope Database

Found 37 matching records:

Displaying record number 59904

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL9
Species (MHC/HLA)	human(B35:02, B35:03, B*53:01)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope, chronic infection

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
KEKGGLEGL had a significantly positive association with HLA B*3502,B*3503,B*5301; it was recognized by 2/33 B*3502,B*3503,B*5301-positive subjects and 1/278 B*3502,B*3503,B*5301-negative subjects.

References

Pereyra2014 Florencia Pereyra, David Heckerman, Jonathan M. Carlson, Carl Kadie, Damien Z. Soghoian, Daniel Karel, Ariel Goldenthal, Oliver B. Davis, Charles E. DeZiel, Tienho Lin, Jian Peng, Alicja Piechocka, Mary Carrington, and Bruce D. Walker. HIV Control Is Mediated in Part by CD8+ T-Cell Targeting of Specific Epitopes. J. Virol., 88(22):12937-12948, Nov 2014. PubMed ID: 25165115. Show all entries for this paper.

Displaying record number 62540

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL9-N
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 KEKGGLEGL-specific CTL clonal response in individual S00016 demonstrated a 0.05 Sorenson similarity index and a mean breadth of 2.5.
Based on all HIV-1 subtype B sequences in LANL HIV Sequence Database at time of analysis, KEKGGLEGL had a Simpson diversity index of 0.51.

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 54578

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
		Show epitope variants
Epitope Name	KL9
Subtype	B
Species (MHC/HLA)	human(B*40)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	Intracellular cytokine staining, Other
Keywords	rate of progression, escape, mutation acquisition

Notes

To correlate evolving HIV-1 populations with HLA-A2 restricted immune responses for epitopes in Gag, Pol, Env and Nef, 11 treatment-naive subjects were longitudinally studied. Results show that increased viral load is often associated with broad CTL responses early in infection that persist as an "immunological footprint". Conversely, early, restricted responses may help limit viral load. Phylogenetic and functional evidence of viral escape is seen in Gag, Nef and Pol. Gag and Nef show flanking epitope changes restricted by non-HLA-A2 alleles. As far as modes of viral adaptation, CTL responses were seen to develop both against static viral populations resulting in viral evolution to HLA-A2 as well as against existing mutants resulting in reselection of consensus B-like variants. This study reinforces that CTL immune responses detected are not necessarily beneficial to patients, but may be "footprints" from early effective responses that the virus has since escaped.
A minor response was detected against an E98D variant of this epitope, KEKGGLdGL.

References

Karlsson2007 Annika C. Karlsson, Astrid K. N. Iversen, Joan M. Chapman, Tulio de Oliviera, Gerald Spotts, Andrew J. McMichael, Miles P. Davenport, Frederick M. Hecht, and Douglas F. Nixon. Sequential Broadening of CTL Responses in Early HIV-1 Infection Is Associated with Viral Escape. PLoS ONE, 2:e225, 2007. PubMed ID: 17311088. Show all entries for this paper.

Displaying record number 55258

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*40)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	assay or method development, optimal epitope

Notes

HLA-A11-restricted CTL epitopes in 2 male Han Chinese subjects (one ART naive and one receiving HAART) were determined. A novel epitope was discovered and 5 other putative epitopes confirmed using 425 overlapping peptides spanning the entire HIV-1 clade B proteome. By employing intracellular cytokine staining, the authors developed a new method of mapping optimal epitopes and defining their HLA restriction efficiently. In spite of its being the most common HLA type in China, A*11-restricted epitopes were recognized less frequently than other epitopes, and A*11-restricted responses formed a mean of only 13% of the responses against HIV.
This epitope, KEKGGLEGL, was detected within overlapping peptide SHFLKEKGGLEGLIYSQK.

References

Wang2007 Shaoyang Wang, Yongtao Sun, Song Zhai, Yan Zhuang, Shuguang Zhao, Whenzhen Kang, Xinhong Li, Dedong Huang, Xu G. Yu, Bruce D. Walker, and Marcus A. Altfeld. Identification of HLA-A11-Restricted HIV-1-Specific Cytotoxic T-Lymphocyte Epitopes in China. Curr. HIV Res., 5(1):119-128, Jan 2007. PubMed ID: 17266563. Show all entries for this paper.

Displaying record number 56413

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL9
Subtype	B
Species (MHC/HLA)	human(B*40)
Immunogen	HIV-1 infection
Country	Australia, Canada, Germany, United States
Experimental methods
Keywords	HLA associated polymorphism

Notes

98 newly infected patients were studied to track early host HLA and Gag/Pol/Nef epitope immune responses' association with viral evolution. Response hierarchies were the same as those for later infection, and 50% of the most rapidly substituting epitopes were restricted by protective HLA, e.g. Gag B*57-associated mutations which were the most rapidly reverting upon transmission to a non-B*57-host. While there are great differences in mutation rates and reversions across the HIV proteome, most early viral change is driven by immune pressure.
HLA-driven epitope evolution was seen in 80% of published CTL epitopes.
HLA-B*40-associated substitutions within optimally defined epitope KEKGGLEGL are at positions E2, E7 and L9, KeKGGLeGl.

References

Brumme2008 Zabrina L. Brumme, Chanson J. Brumme, Jonathan Carlson, Hendrik Streeck, Mina John, Quentin Eichbaum, Brian L Block, Brett Baker, Carl Kadie, Martin Markowitz, Heiko Jessen, Anthony D. Kelleher, Eric Rosenberg, John Kaldor, Yuko Yuki, Mary Carrington, Todd M. Allen, Simon Mallal, Marcus Altfeld, David Heckerman, and Bruce D. Walker. Marked Epitope- and Allele-Specific Differences in Rates of Mutation in Human Immunodeficiency Type 1 (HIV-1) Gag, Pol, and Nef Cytotoxic T-Lymphocyte Epitopes in Acute/Early HIV-1 Infection. J. Virol., 82(18):9216-9227, Sep 2008. PubMed ID: 18614631. Show all entries for this paper.

Displaying record number 57393

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	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 BV07, BV6a, BV20 and BV05b 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 57559

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location
Epitope	`KEKGGLEGL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*40)
Immunogen	HIV-1 infection
Patient MHC/HLA	MM50: A02, A03, B13, B40, C03, C06
Country	United Kingdom
Experimental methods	Tetramer binding
Keywords	dynamics, acute/early infection, assay or method development

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.
Longitudinal analysis of surface PD-1 expression, a marker of T cell exhaustion, was performed for this epitope, revealing that a proportion of HIV tetramer+ cells was already PD-1 at the first sampling time point, and then proportion of cells expressing PD-1 changed in a pattern that closely followed the response magnitude over time as shown for patient MM50 in Fig. 6 of Turnbull2009.
As indicated in parentheses, other patients had CTL responses to peptides or epitopes that overlap or contain KEKGGLEGL: B cons peptides YKAAVDLSHFLKEKGGLEGL (MM23 & MM46) & LKEKGGLEGLIYSQKRQDIL (MM50), autologous peptides FFLKEKGGLEGLIHSQKR (MM43) & YKGAVDLSHFLKEKGGLE (MM33) and epitope FLKEKGGL (MM13). Dynamics of these responses and peptide sequences are shown in Fig. S1-S3 of Yang2019 which developed mathematical models with the Turnbull2009 dataset.

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. 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 58548

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	B40-KL9
Subtype	B
Species (MHC/HLA)	human(B*40)
Immunogen	HIV-1 infection
Country	United States
Experimental methods
Keywords	review, rate of progression, acute/early infection

Notes

Acute infection with HIV-1 is accompanied by high viral load (VL) and loss of CD4 helper T cells. Early inhibition of VL by CTL results in a 'set point' that is correlated with disease progression. The early CTL response during acute infection if successful is to a known immunodominant epitope. Following, chronic infection sets in with a greater breadth and magnitude of CTL response, but no change in VL or HIV-1 replication. Immunodominant epitopes from several studies that help set a lower VL during acute phase are listed in this review.
KEKGGLEGL, B40-KL9, when restricted by HLA-B*40 is recognized by 64% acutely-infected and 43% chronically-infected North American subjects expressing the same HLA allele. HLA-B*40 is present at a frequency of 14.7% in North American white populations.

References

Streeck2010 Hendrik Streeck and Douglas F. Nixon. T Cell Immunity in Acute HIV-1 Infection. J. Infect. Dis., 202(Suppl 2):S302-8, 15 Oct 2010. PubMed ID: 20846037. Show all entries for this paper.

Displaying record number 58764

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	Nef-KL9
Subtype	B
Species (MHC/HLA)	human(B*40)
Immunogen	HIV-1 infection
Country	Australia, Canada, United States
Experimental methods	Chromium-release assay
Keywords	class I down-regulation by Nef

Notes

Factors impacting Nef-mediated immune evasion were studied using 17 epitopes and the kinetics of infected cell clearance. Recognition and clearance of infected presenting cells by Gag-specific CTL is dependent upon the specific epitope it presents as well as virus inoculum (multiplicity of infection, moi), but not on the particular restricting HLA or on any kinetic advantage for early expressed proteins like Rev, Tat and Nef.
HLA-B*40-restricted Nef-KL90-specific CTL were used in this study.

References

Chen2012 Diana Y. Chen, Arumugam Balamurugan, Hwee L. Ng, William G. Cumberland, and Otto O. Yang. Epitope Targeting and Viral Inoculum Are Determinants of Nef-Mediated Immune Evasion of HIV-1 from Cytotoxic T Lymphocytes. Blood, 120(1):100-111, 5 Jul 2012. PubMed ID: 22613796. Show all entries for this paper.

Displaying record number 58806

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
		Show epitope variants
Epitope Name	KL9
Subtype	A, B, C, CRF01_AE, D, F, G, H
Species (MHC/HLA)	human(B*40)
Immunogen	HIV-1 infection
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Degranulation, CD107a and b cell surface mobilization
Keywords	subtype comparisons, epitope processing

Notes

2 Nef epitopes, FL8, FLKEKGGL and KL9, KEKGGLEGL, that overlap by 6 residues but are restricted by different HLAs (B*08 and B*40, respectively), were studied to follow the impact of extremely small shifts in position on epitope processing. Epitope-specific CTLs were tested for recognition of HLA-B*40- or B*08-restricted Nef epitopes (KL9 or FL8) from different HIV isolates. The different subtypes all carried the same epitope sequences but had minor differences in flanking sequences. Each epitope was recognized to a different extent depending on what its subtype was, and this was dependent on flanking sequences.
The same KL9 sequence from different subtypes (clades B, D, AE, F), was recognized to different extents; and KL9-7D, KEKGGLDGL, from clades A, B, G and H were also recognized to varying extents.

References

Culshaw2012 Abigail Culshaw, Tao Dong, and Sarah Louise Rowland-Jones. A 2 Amino Acid Shift in Position Leads to a Substantial Difference in the Pattern of Processing of 2 HIV-1 Epitopes. J. Acquir. Immune Defic. Syndr., 59(4):335-339, 1 Apr 2012. PubMed ID: 22217677. Show all entries for this paper.

Displaying record number 59902

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL9
Species (MHC/HLA)	human(B*40)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope, chronic infection

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
KEKGGLEGL had a significantly positive association with HLA B*40; it was recognized by 11/28 B*40-positive subjects and 4/313 B*40-negative subjects.

References

Displaying record number 55088

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL-9
Species (MHC/HLA)	human(B40)
Immunogen	HIV-1 infection
Experimental methods
Keywords	escape, TCR usage, mutation acquisition

Notes

The dependence of TCR clonotype recruitment on genetic background was determined by studying monozygotic twins infected with the same HIV-1 strain. After an early, initial correlation in the magnitude, specificity and immunodominance of CTL response [Draenert et al. J. Exp. Med. 203:529-539(2006)], subsequent disease was mixed with respect to CTL epitopes' mutational escape. TCR alpha and beta chain repertoires were analyzed and it was found that their clonotypes in HIV-specific CTLs were broadly heterogeneous for both concordant and discordant epitope sequence evolution between the twins. Therefore initial TCR recruitment appears to be an entirely random process independent of genetic background of the infected individual.
This epitope, KL9, showed concordant epitope evolution between the twins, but both alpha and beta TCR chains recruited were entirely different between them.

References

Yu2007 Xu G. Yu, Mathias Lichterfeld, Katie L. Williams, Javier Martinez-Picado, and Bruce D. Walker. Random T-Cell Receptor Recruitment in Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ T Cells from Genetically Identical Twins Infected with the Same HIV-1 Strain. J Virol, 81(22):12666-12669, Nov 2007. PubMed ID: 17804503. Show all entries for this paper.

Displaying record number 55204

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location
Epitope	`KEKGGLEGL`	Epitope Alignment
Species (MHC/HLA)	human(B40)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	supertype, HLA cross-presentation

Notes

100 HIV-infected subjects were tested for response to optimally-defined CTL epitopes regardless of the subject's HLA type. Half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Statistical and experimental methods were used to define additional HLA alleles associated with the epitopes.
In addition to its known HLA association (B40), an additional HLA (B49) was statistically predicted to be associated with this epitope.

References

Frahm2007b Nicole Frahm, Karina Yusim, Todd J. Suscovich, Sharon Adams, John Sidney, Peter Hraber, Hannah S. Hewitt, Caitlyn H. Linde, Daniel G. Kavanagh, Tonia Woodberry, Leah M. Henry, Kellie Faircloth, Jennifer Listgarten, Carl Kadie, Nebojsa Jojic, Kaori Sango, Nancy V. Brown, Eunice Pae, M. Tauheed Zaman, Florian Bihl, Ashok Khatri, Mina John, Simon Mallal, Francesco M. Marincola, Bruce D . Walker, Alessandro Sette, David Heckerman, Bette T. Korber, and Christian Brander. Extensive HLA Class I Allele Promiscuity among Viral CTL Epitopes. Eur. J. Immunol., 37(9):2419-2433, Sep 2007. PubMed ID: 17705138. Show all entries for this paper.

Displaying record number 55512

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL9
Subtype	B
Species (MHC/HLA)	human(B40)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Tetramer binding
Keywords	dynamics, characterizing CD8+ T cells, chronic infection

Notes

T-cells were studied for exhaustion and dysfunction in chronic HIV infection. Polyfunctionality of CTL immune response to HIV-1 decreased with persistence of antigen presence over time in chronic infection. CTL exhaustion can thus be halted by reduction in viral antigen load - either by ART or through escape mutations.
PD-1, marker for activation and apoptosis increases over time, but it decreases when epitope mutations develop. CD127 however, is not impacted by viral escape.
Epitope KEKGGLEGL varied to rEKGGLEGL in an untreated patient, Ac-83. Previously published HLA-restriction for KL9 is HLA-B40.

References

Streeck2008 Hendrik Streeck, Zabrina L. Brumme, Michael Anastario, Kristin W. Cohen, Jonathan S. Jolin, Angela Meier, Chanson J. Brumme, Eric S. Rosenberg, Galit Alter, Todd M. Allen, Bruce D. Walker, and Marcus Altfeld. Antigen Load and Viral Sequence Diversification Determine the Functional Profile of HIV-1-Specific CD8+ T Cells. PLoS Med, 5(5):e100, 6 May 2008. PubMed ID: 18462013. Show all entries for this paper.

Displaying record number 54363

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	B40-KL9(Nef)
Species (MHC/HLA)	human(B40)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, immunodominance, early-expressed proteins

Notes

Immunodominant HIV epitopes in early, primary infection of CTLs were identified and the relative contributions of immune responses restricted to individual HLA class I molecules were studied.
This epitope-HLA combination was recognized. The most frequently recognized epitopes also elicited the greatest CTL response.
HIV-1 Epitope sequence variability was not correlated with immunodominant versus immune sub-dominant responses.
HLA-B*57 and HLA-B*27 restricted responses were the strongest in these early and acute infections - due to dominant responses to a single epitope in each case (TW10 for B*57 and KK10 for B*27).
In the presence of HLA-B*57 and HLA-B*27 restricted responses, the relative contributions of other restricting HLA dropped greatly.

References

Altfeld2006 Marcus Altfeld, Elizabeth T. Kalife, Ying Qi, Hendrik Streeck, Mathias Lichterfeld, Mary N. Johnston, Nicole Burgett, Martha E. Swartz, Amy Yang, Galit Alter, Xu G. Yu, Angela Meier, Juergen K. Rockstroh, Todd M. Allen, Heiko Jessen, Eric S. Rosenberg, Mary Carrington, and Bruce D. Walker. HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8+ T Cell Response against HIV-1. PLoS Med., 3(10):e403, Oct 2006. PubMed ID: 17076553. Show all entries for this paper.

Displaying record number 56035

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL9(Nef)
Subtype	B
Species (MHC/HLA)	human(B40)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	chronic infection

Notes

49 ART-naive chronically HIV-1 infected Chinese subjects' CTLs were tested with 413 OLPs in IFN-γ assays, determining optimal epitopes specific for Chinese Clade B HIV-1 sequences.
An inverse correlation was found between CTL response and viral load.
Targeted peptides have lower entropy than peptides that are not CTL targeted. This correlation is independent of HLA-restriction.
HLA-B40-restricted epitope KEKGGLEGL elicited an immune response in Chinese HIV-1 positive subjects as part of peptide SHFLKEKGGLEGLIYSQK.
11 of the 20 HLA-B40 carriers responded to KEKGGLEGL-containing peptide with average magnitude of CTL response of 321 SFC/million PBMC (author communication and Fig.1).

References

Zhai2008 Song Zhai, Yan Zhuang, Yang Song, Shu Li, Dedong Huang, Wenzhen Kang, Xinhong Li, Qi Liao, Yanhou Liu, Zhongfang Zhao, Yichen Lu, and Yongtao Sun. HIV-1-Specific Cytotoxic T Lymphocyte (CTL) Responses Against Immunodominant Optimal Epitopes Slow the Progression of AIDS in China. Curr. HIV Res., 6(4):335-350, Jun 2008. PubMed ID: 18691032. Show all entries for this paper.

Displaying record number 57820

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*40:01)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	computational epitope prediction, HLA associated polymorphism

Notes

From a large study of HLA-associated polymorphisms, 431 putative epitopes with good EpiPred scores were selected; 320 of these were tested for IFNgamma EliSpot responses in subjects carrying the predicted HLA.
Peptides with response rate >40% (comparable with mean response rate of 33% for known epitopes) and tested in 5 or more individuals with respective HLA were considered in this study as probable novel epitopes and entered in the database. 41 additional "possible" novel epitopes for which either <5 individuals were tested or response rate was below 40%, are not entered in the database.
There was a markedly higher proportion of putative epitopes in Nef, and the Nef epitopes tended to have the most high-magnitude EliSpot responses. Among 33 epitopes that elicited a response in over 40% out of 5 or more individuals tested, over 61% clustered in Nef.
Epitope KEKGGLEGL was recognized by 4/5 B*4001-positive HIV-1-infected patients.

References

Almeida2011 Coral-Ann M. Almeida, Corine Bronke, Steven G. Roberts, Elizabeth McKinnon, Niamh M. Keane, Abha Chopra, Carl Kadie, Jonathan Carlson, David W. Haas, Sharon A. Riddler, Richard Haubrich, David Heckerman, Simon Mallal, and Mina John. Translation of HLA-HIV Associations to the Cellular Level: HIV Adapts to Inflate CD8 T Cell Responses against Nef and HLA-Adapted Variant Epitopes. J. Immunol., 187(5):2502-2513, 1 Sep 2011. PubMed ID: 21821798. Show all entries for this paper.

Displaying record number 58245

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(99-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(B*40:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	MM43: A02, A02:01, B40:01, B55:01, C03, C03
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 FFLKEKGGLEGLIHSQKR (Nef 89-106) contains epitope KEKGGLEGL, that shows evidence of late escape or variation from 552 days from onset of symptoms (DFOSx) onwards. This epitope elicited CTL responses in patient MM43.

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 55067

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL9
Species (MHC/HLA)	human(B*40:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A02:01, A24:02, B40:01, B50:01, C*03, Cw4
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	immunodominance, escape, variant cross-reactivity

Notes

HIV-specific cellular and humoral immune responses were examined in monozygotic male twins infected simultaneously with the same virus. 15 of 17 targeted epitopes were identical in the twins, including two immunodominant responses. 3 of 4 declining responses in the twins showed mutations at the same residue. Evolving antibody responses cross-neutralized the other twin's virus. The results were compared with a third brother, infected by the twins' virus 13 months after their seroconversion. The data show similarity in disease course in persons of identical genetic background infected with the same strain of HIV-1.
This epitope, KEKGGLEGL (KL9) restricted by HLA-B*4001, was one of two immunodominant responses.

References

Draenert2006 Rika Draenert, Todd M. Allen, Yang Liu, Terri Wrin, Colombe Chappey, Cori L. Verrill, Guillem Sirera, Robert L. Eldridge, Matthew P. Lahaie, Lidia Ruiz, Bonaventura Clotet, Christos J. Petropoulos, Bruce D. Walker, and Javier Martinez-Picado. Constraints on HIV-1 Evolution and Immunodominance Revealed in Monozygotic Adult Twins Infected with the Same Virus. J. Exp. Med., 203(3):529-539, 20 Mar 2006. PubMed ID: 16533886. Show all entries for this paper.

Displaying record number 53786

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL9
Species (MHC/HLA)	(B*40:01)
Immunogen
Experimental methods
Keywords	review, immunodominance, escape, acute/early infection, early-expressed proteins, kinetics, viral fitness and reversion

Notes

This review discusses the importance of 3 factors that impact the selection of immunodominant epitopes in acute HIV infection: i) the kinetics of viral protein expression, ii) the HLA class I background of the infected individual, and iii) the autologous sequence of the infecting virus. This is 1 of 12 peptides listed as immunodominant in acute HIV-1 infection.

References

Lichterfeld2005 Mathias Lichterfeld, Xu G. Yu, Sylvie Le Gall, and Marcus Altfeld. Immunodominance of HIV-1-Specific CD8+ T-Cell Responses in Acute HIV-1 Infection: At the Crossroads of Viral and Host Genetics. Trends Immunol., 26(3):166-171, Mar 2005. PubMed ID: 15745859. Show all entries for this paper.

Displaying record number 60964

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*40:01)
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.
KEKGGLEGL, restricted by B*4001, 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 1021

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	( LAI)
Epitope	`KEKGGLEGL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*40:01)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is a B*4001,B60 epitope.

References

Llano2019 Anuska Llano, Samandhy Cedeño, Sandra Silva Arrieta, and Christian Brander. The 2019 Optimal HIV CTL Epitopes Update: Growing Diversity in Epitope Length and HLA restriction. 2019. Show all entries for this paper.

Displaying record number 1963

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	Nef-KL9
Subtype	B
Species (MHC/HLA)	human(B*40:02)
Immunogen	HIV-1 infection
Patient MHC/HLA	01RCH59: A02:01, A32:01, B40:02, B53:01, C02:02, C04:01
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	novel epitope

Notes

This study monitored epitope responses in HIV-1 infected minority women living in the United States.
24 epitopes were described -- 8 were novel, 8 used new restricting elements but were previously defined epitopes, and 8 were previously described. This epitope was previously described as restricted by B*4001. Here are novel restriction, B*4002 is identified.
Serial peptide truncations were used to define optimal epitopes for CTL cell lines isolated from 12 individuals, assayed by a Cr-release.
Patient 01RCH59 was Hispanic, not on HAART, and had a viral load of 5,100 and CD4 count of 349 -- she also recognized TERQANFL, p2p7p1p6(64-70), HLA-B*4002 and AEWDRVHPV, p24(78-86), HLA-B*4002.
Among HIV+ individuals who carried HLA B40, 3/5 (60%) recognized this epitope.

References

Sabbaj2003 Steffanie Sabbaj, Anju Bansal, G. Douglas Ritter, Christopher Perkins, Bradley H. Edwards, Ethan Gough, Jianming Tang, James J. Szinger, Bette Korber, Craig M. Wilson, Richard A. Kaslow, Mark J. Mulligan, and Paul A. Goepfert. Cross-Reactive CD8+ T Cell Epitopes Identified in US Adolescent Minorities. J. Acquir. Immune Defic. Syndr., 33(4):426-438, 1 Aug 2003. PubMed ID: 12869831. Show all entries for this paper.

Displaying record number 52572

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Species (MHC/HLA)	human(B*40:02)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

References

Displaying record number 56483

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*44:03)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	viral fitness and reversion, HLA associated polymorphism

Notes

HLA-associated polymorphisms were studied in a cohort of 710 chronic subtype C patients from South Africa. 84 HLA Class I-associated polymorphisms were identified, 73% of them with HLA-B. The viral set points associated with HLA allele correlated with the number of reversions associated with that allele, (HLA-B in Gag, HLA-C in Pol).
RPQVPLRPM is a previously described HLA-B*4403-restricted epitope (part of Nef reacting peptides AAFDLSFFLKeKGGLEGLIYS and KEKGGLEGLIySKKRQEILDL) that contain a B*4403-associated reversion at residue E (KeKGGLEGL).

References

Matthews2008 Philippa C. Matthews, Andrew Prendergast, Alasdair Leslie, Hayley Crawford, Rebecca Payne, Christine Rousseau, Morgane Rolland, Isobella Honeyborne, Jonathan Carlson, Carl Kadie, Christian Brander, Karen Bishop, Nonkululeko Mlotshwa, James I. Mullins, Hoosen Coovadia, Thumbi Ndung'u, Bruce D. Walker, David Heckerman, and Philip J. R. Goulder. Central Role of Reverting Mutations in HLA Associations with Human Immunodeficiency Virus Set Point. J. Virol., 82(17):8548-8559, Sep 2008. PubMed ID: 18596105. Show all entries for this paper.

Displaying record number 56604

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(91-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL9
Subtype	C
Species (MHC/HLA)	human(B*44:03)
Immunogen	HIV-1 infection
Country	South Africa, Zambia
Experimental methods
Keywords	viral fitness and reversion, HLA associated polymorphism

Notes

A cohort of clade C-infected Zambian HIV-1 transmission pairs was studied. Accumulation in the donor of HLA-B restricted mutations in Gag, but not in Nef resulted in a reduced viral load in a recipient upon transmission.
20 mutations in Gag and 11 mutations in Nef, within or flanking CTL epitopes, were considered based on data from a Clade C South African cohort. HLA-B*4403-restricted KEKGGLEGL (KL9) was associated with a polymorphism flanking KL9 at FFLKEKGGLEGLI(Y)S.

References

Goepfert2008 Paul A. Goepfert, Wendy Lumm, Paul Farmer, Philippa Matthews, Andrew Prendergast, Jonathan M. Carlson, Cynthia A. Derdeyn, Jianming Tang, Richard A. Kaslow, Anju Bansal, Karina Yusim, David Heckerman, Joseph Mulenga, Susan Allen, Philip J. R. Goulder, and Eric Hunter. Transmission of HIV-1 Gag Immune Escape Mutations Is Associated with Reduced Viral Load in Linked Recipients. J. Exp. Med., 205(5):1009-1017, 12 May 2008. PubMed ID: 18426987. Show all entries for this paper.

Displaying record number 59903

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL9
Species (MHC/HLA)	human(B*55)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope, chronic infection

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
KEKGGLEGL had a significantly positive association with HLA B*55; it was recognized by 1/2 B*55-positive subjects and 3/311 B*55-negative subjects.

References

Displaying record number 1813

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Species (MHC/HLA)	human(B60, B61)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

No immunodominant responses were detected to five B*61-restricted epitopes tested.
All five B*60-restricted epitopes were reactive in another subject, and the B*60-restricted responses together contributed over one-third of the total CTL response.

References

Day2001 C. L. Day, A. K. Shea, M. A. Altfeld, D. P. Olson, S. P. Buchbinder, F. M. Hecht, E. S. Rosenberg, B. D. Walker, and S. A. Kalams. Relative dominance of epitope-specific cytotoxic T-lymphocyte responses in human immunodeficiency virus type 1-infected persons with shared HLA alleles. J. Virol., 75(14):6279-91, Jul 2001. URL: http://jvi.asm.org/cgi/content/full/75/14/6279. PubMed ID: 11413294. Show all entries for this paper.

Displaying record number 53154

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100)
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	Nef KL9
Subtype	B
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Experimental methods	Chromium-release assay, Flow cytometric T-cell cytokine assay
Keywords	binding affinity, TCR usage, characterizing CD8+ T cells

Notes

Killing efficiency of CTLs and their ability to suppress viral replication is shown to depend more on epitope specificity than to antigenic avidity. Different clones recognizing the same epitope had similar killing efficiency despite their variation in avidity. Nef specific CTL clones tended to be most inhibitory, followed by Gag, then by RT specific clones, regardless of avidity.
2/14 CTL T-cell clones tested were specific for Nef KL9. Under conditions of excess peptide (100ug/ml), there was no difference in their lytic potential; all possessed similar effector capacity. Avidity was measured as the sensitizing dose of peptide required for 50% of maximal killing (SD50), which varied from 20 pg/ml to 100 ng/ml, over four orders of magnitude for all 14 epitopes. The SD50 range for Nef KL9 was 20-30 pg/ml, both high avidity. These clones were among the most efficient at inhibiting viral replication in the set tested, but because of the general lack of correlation between avidity and viral inhibition efficiency in this study, the authors attribute other reasons to Nefs ability to inhibit viral replication that pertain to presentation like kinetics and expression levels.

References

Yang2003a Otto O. Yang, Phuong T. Nguyen Sarkis, Alicja Trocha, Spyros A. Kalams, R. Paul Johnson, and Bruce D. Walker. Impacts of Avidity and Specificity on the Antiviral Efficiency of HIV-1-Specific CTL. J. Immunol., 171(7):3718-3724, 1 Oct 2003. PubMed ID: 14500671. Show all entries for this paper.

Displaying record number 1528

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(90-98 SF2)
Epitope	`KEKGGLEGL`	Epitope Alignment
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, acute/early infection

Notes

Therapy provided during acute infection resulted in a narrower CTL response, stronger T help response, and a less diverse viral population than was seen in individuals treated during chronic infection.
The breadth and specificity of the response was determined using ELISPOT by studying 19 individuals with pre-seroconversion therapy (Group 1), 11 individuals with primary infection but post-seroconversion therapy (Group 2), and 10 individuals who responded to HAART given during chronic infection (Group 3), using 259 overlapping peptides spanning p17, p24, RT, gp41, gp120 and Nef.
Previously described and newly defined optimal epitopes were tested for CTL response.
Number of HLA-B60+ individuals that had a CTL response to this epitope broken down by group: 2/2 group 1, 1/1 group 2, and 0/0 group 3.

References

Altfeld2001b M. Altfeld, E. S. Rosenberg, R. Shankarappa, J. S. Mukherjee, F. M. Hecht, R. L. Eldridge, M. M. Addo, S. H. Poon, M. N. Phillips, G. K. Robbins, P. E. Sax, S. Boswell, J. O. Kahn, C. Brander, P. J. Goulder, J. A. Levy, J. I. Mullins, and B. D. Walker. Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J. Exp. Med., 193(2):169-80, 15 Jan 2001. URL: http://www.jem.org/cgi/content/full/193/2/169. PubMed ID: 11148221. Show all entries for this paper.

Displaying record number 1839

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef( SF2)
Epitope	`KEKGGLEGL`	Epitope Alignment
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

This epitope was the dominant B60 (encoded by B*4001) response in 6/8 HLA-B60 individuals, and recognized in all eight.
This epitope was also recognized two expressing HLA-B61 individuals (B61 is usually encoded by B*4002, but this study did not distinguish between B*4002, B*4003, B*4004, B*4006, and B*4008)
ELISPOT was a rapid an effective method that was used to define five novel B60 epitopes.
HLA-B60 is present in 10-20% of the Caucasoid population and B60/B61 are very common in Asian populations.

References

Altfeld2000 M. A. Altfeld, A. Trocha, R. L. Eldridge, E. S. Rosenberg, M. N. Phillips, M. M. Addo, R. P. Sekaly, S. A. Kalams, S. A. Burchett, K. McIntosh, B. D. Walker, and P. J. Goulder. Identification of dominant optimal HLA-B60- and HLA-B61-restricted cytotoxic T-lymphocyte (CTL) epitopes: rapid characterization of CTL responses by enzyme-linked immunospot assay. J. Virol., 74:8541, 2000. PubMed ID: 10954555. Show all entries for this paper.

Displaying record number 52110

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Experimental methods
Keywords	epitope processing

Notes

KM is a B60 restricted CTL clone that recognizes KEKGGLEGL.
CTL could be activated by a fusion protein of an HIV protein and anthrax lethal factor (LFn-HIV) that promotes antigen presenting cell uptake of exogenous protein and allows processing through the MHC class I pathway. This strategy for CTL detection could allow antigen presentation without generation of cells by the standard methods of using live viral vectors carrying a protein, or by loading the cells with peptides and by-passing processing.

References

Cao2002 Huyen Cao, Deepak Agrawal, Nicholas Kushner, Neal Touzjian, Max Essex, and Yichen Lu. Delivery of exogenous protein antigens to major histocompatibility complex class I pathway in cytosol. J. Infect. Dis., 185(2):244-251, 15 Jan 2002. PubMed ID: 11807699. Show all entries for this paper.

Displaying record number 52516

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100 NL-43)
Epitope	`KEKGGLEGL`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Experimental methods
Keywords	class I down-regulation by Nef, escape

Notes

NL43 was passaged in the presence of Nef KEKGGLEGL-specific CTL clones STD11 and KM3, giving rise to rapid selection of escape mutations, including E93G, E93K, K94N+G99R, G95R+G99R, E98K, E98D, G99R, G99E, L100P, and L100I; insertions, deletions, frameshifts and an early stop codon. 34/36 (94%) of sequences carried mutations in the epitope by seven days, 36/36 (100%) by 14 days.
NL43 was also passaged in the presence of a Nef TQGYFPDWQNY-specific CTL clone. 7/15 clones had a frameshifting or stop codon introduced by one week; F121T was also observed. The most common escape mutation for both Nef epitopes was an early stop codon at position 91.
Several mutations selected by KEKGGLEGL-specific CTL were shown to impair the down regulation of class I MHC by Nef, in particular E93G, E93K, and a truncation mutation at position 51.
Nef deletion mutants increased 100-fold NL-43 susceptibility to inhibition by CTL specific for epitopes in other proteins, the A2 epitopes ILKEPVHGV in RT and SLYNTVATL in p17 Gag.

References

Ali2003 Ayub Ali, Satish Pillai, Hwee Ng, Rachel Lubong, Douglas D. Richman, Beth D. Jamieson, Yan Ding, M. Juliana McElrath, John C. Guatelli, and Otto O. Yang. Broadly Increased Sensitivity to Cytotoxic T Lymphocytes Resulting from Nef Epitope Escape Mutations. J. Immunol., 171(8):3999-4005, Oct 2003. PubMed ID: 14530319. Show all entries for this paper.

Displaying record number 53380

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	( B consensus)
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL10
Subtype	B
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, B14, B60, Cw3, Cw7
Experimental methods	Chromium-release assay, Cytokine production, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	assay or method development, memory cells, characterizing CD8+ T cells

Notes

Using a flow-cytometric cytotoxicity assay based on caspase-3 activation in dying target cells, it was shown that the subset of HIV-1-specific CD8+ T cells secreting both IFN-gamma and TNF-alpha exhibit stronger cytotoxic activity than those secreting only IFN-gamma. These cells also exhibited stronger intracellular perforin expression. No association between HIV-1-specific CD8+ T-cell maturation phenotypes and intracellular perforin expression was found.
1/9 individuals recognized this epitope; the authors write that it is presented by HLA-B40 in their Table 1, but the subject that recognizes it, AC05, is HLA-B60, so we assume they meant B60.

References

Lichterfeld2004b Mathias Lichterfeld, Xu G. Yu, Michael T. Waring, Stanley K. Mui, Mary N. Johnston, Daniel Cohen, Marylyn M. Addo, John Zaunders, Galit Alter, Eunice Pae, Daryld Strick, Todd M. Allen, Eric S. Rosenberg, Bruce D. Walker, and Marcus Altfeld. HIV-1-Specific Cytotoxicity Is Preferentially Mediated by a Subset of CD8+ T Cells Producing both Interferon-gamma and Tumor Necrosis Factor-alpha. Blood, 104(2):487-394, 15 Jul 2004. PubMed ID: 15059848. Show all entries for this paper.

Displaying record number 52745

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
Epitope Name	KL9
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A24, B38, B60, C*12, Cw2
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	supervised treatment interruptions (STI), early treatment

Notes

HIV-1+ patient AC10 underwent early HAART treatment, which was discontinued 1.5 years later. At this timepoint potent NAb responses against autologous virus were detected. Treatment interruption initially induced weak CD8+ responses directed against 5 epitopes. By days 873d and 923d the CTL response had broadened to target 22 epitopes; of these six were fully characterized. Eventually the virus escaped the NAb response, but escape was not accompanied by a rise in viral load, and the authors suggest the virus was contained by the CTL response.

References

Montefiori2003 David C. Montefiori, Marcus Altfeld, Paul K. Lee, Miroslawa Bilska, Jintao Zhou, Mary N. Johnston, Feng Gao, Bruce D. Walker, and Eric S. Rosenberg. Viremia Control Despite Escape from a Rapid and Potent Autologous Neutralizing Antibody Response after Therapy Cessation in an HIV-1-Infected Individual. J. Immunol., 170(7):3906-3914, Apr 2003. PubMed ID: 12646660. Show all entries for this paper.

Displaying record number 52790

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef(92-100 NL43)
Epitope	`KEKGGLEGL`	Epitope Alignment
		Show epitope variants
Epitope Name	KL9
Subtype	B
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Experimental methods	CTL suppression of replication, Chromium-release assay
Keywords	escape

Notes

Virus was cultured in the presence of CTL lines specific for 5 different epitopes (SLYNTVATL, ILKEPVHGV, IEIKDTKEAL, SEGATPQDL, and KEKGGLEGL) to study the emergence of escape mutations. Escape varied between clones for the same epitope, and between different epitopes. Gag and RT epitope escape, if it occurred at all, tended to be monoclonal and within the epitope, indicating strong fitness constraints, while the Nef epitope escape was rapid, polyconal, and sometimes the result of upstream frameshifts.
Two cloned CTL lines recognized KEKGGEGL, STD11 and KM3. Highly resistant clones emerged after a single round of passage with both CTL clones, and multiple substitutions accrued including frameshits and stop codons, reflecting the dispensability of Nef in viral culture.
The following epitope variants were observed after passaging with clone STD11 for one week: kekggegI, kKkggegl, and 12/20 frameshifts and 1 early stop. By two weeks, a more complex polyclonal mixture was observed including: kekggegI, kKkggegl kekggegP, kekggeEl, kekggeRl, kekRgeRl, keNggeRl, and 11/22 frameshifts.

References

Yang2003 Otto O Yang, Phuong Thi Nguyen Sarkis, Ayub Ali, Jason D Harlow, Christian Brander, Spyros A Kalams, and Bruce D Walker. Determinant of HIV-1 Mutational Escape from Cytotoxic T Lymphocytes. J. Exp. Med., 197(10):1365-1375, May 2003. PubMed ID: 12743169. Show all entries for this paper.

Displaying record number 57501

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HXB2 Location	Nef(92-100) DNA(9070..9096)	Nef Epitope Map
Author Location	Nef
Epitope	`KEKGGLEGL`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Australia
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	assay or method development, HLA associated polymorphism, chronic infection

Notes

Standard overlapping subtype B peptides were compared with 'polyallelic peptides' to determine which set could detect a broader range of ELISpot responses. 28 subjects with chronic AIDS were used to test the peptides against protein Nef. Polyallelic peptides were chosen based on relevant epitopes correlating with HLA-restriction and distribution within a subject-population and HLA class I allele-specific polymorphisms of such epitopes were synthesized.
49 overlapping Nef 15-mers were used as the standard peptides. 62 8- to 11-mer peptides were synthesized as the polyallelic set, 24 of which were embedded within the overlapping 15-mers. 61% of patients responded to polyallelic peptides. 7 of 13 'adapted' polyallelic epitopes (i.e. variant optimized epitopes that still might elicit response based on predicted HLA-bindings), elicited responses in >20% of responding subjects. Only 9 of the 62 polyallelic peptides were discussed in the paper though 80% of them elicited CTL response.
Of the 9 non-adapted central Nef epitopes that were part of the polyallelic peptide set, only 2 were able to elicit CTL response. This epitope, KEKGGLEGL, did not elicit a response in any of the responding subjects.

References

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