Search CTL/CD8+ T-Cell Epitope Database

Found 28 matching records:

Displaying record number 60028

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	Pol(330-338)
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	NQY9
Species (MHC/HLA)	human(A*36)
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.
NPDIVIYQY had a significantly positive association with HLA A*36; it was recognized by 1/9 A*36-positive subjects and 0/241 A*36-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 60026

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	Pol(330-338)
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	NQY9
Species (MHC/HLA)	human(B*18)
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.
NPDIVIYQY had a significantly positive association with HLA B*18; it was recognized by 2/18 B*18-positive subjects and 1/250 B*18-negative subjects.

References

Displaying record number 60027

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	Pol(330-338)
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	NQY9
Species (MHC/HLA)	human(B*27)
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.
NPDIVIYQY had a significantly positive association with HLA B*27; it was recognized by 3/36 B*27-positive subjects and 3/268 B*27-negative subjects.

References

Displaying record number 57586

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT(175-183)
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	NY9
Subtype	B
Species (MHC/HLA)	(B*35)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

Responses to specific B57/58, B27, and B35-restricted epitopes were tested in a cohort of 45 subjects during primary infection. The presence of certain B57/58, B27, and B35-restricted T-cell responses during primary infection better defined disease progression than the HLA genotype alone, suggesting that it is the HIV-specific CD8+ T-cells and not the presence of a particular HLA allele, that determine disease progression.
9/20 B35-positive subjects responded to NPDIVIYQY, and 11% of the patients' total response magnitude was derived from this specific response.
This epitope was 24% conserved among M-group sequences and 66% conserved among B-subtype sequences.
While numerous, the NY9 responses did not demonstrate a significant effect on HIV-1 disease progression.

References

Dinges2010 Warren L. Dinges, Julia Richardt, David Friedrich, Emilie Jalbert, Yi Liu, Claire E. Stevens, Janine Maenza, Ann C. Collier, Daniel E. Geraghty, Jeremy Smith, Zoe Moodie, James I. Mullins, M. Juliana McElrath, and Helen Horton. Virus-Specific CD8+ T-Cell Responses Better Define HIV Disease Progression than HLA Genotype. J. Virol., 84(9):4461-4468, May 2010. PubMed ID: 20147397. Show all entries for this paper.

Displaying record number 56392

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT(175-183)
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	NY9
Subtype	B
Species (MHC/HLA)	human(B*35)
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.
HLAs-B*35-associated substitution within optimally defined epitope NPDIVIYQY is at position D3, NPdIVIYQY.

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 1560

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT(175-183 SF2)
Epitope	`NPDIVIYQY`	Epitope Alignment
Species (MHC/HLA)	human(B35)
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-B35+ individuals that had a CTL response to this epitope broken down by group: 1/2 group 1, 0/2 group 2, and 1/1 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 52255

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	Pol
Epitope	`NPDIVIYQY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Patient MHC/HLA	A11, A3, B35, B51
Experimental methods
Keywords	mother-to-infant transmission

Notes

IFNgamma T-cell responses in breast milk of 5 HIV-1 infected women from the US and 6 from Zambia were tested with using Elispot. 11/11 women responded to Gag, 8/11 responded to Pol, 7/11 women to Nef, and 2/5 women to Env peptide pools. These responses were shown to be primarily due to CD8+ T-cells in one woman, and another woman had cytolytic responses measured by Cr-release.
T-cells in breast milk from a volunteer who was HLA A3, A11, B35, B51 induced IFNgamma after stimulation with a peptide that carries known B35 epitope NPDIVIYQY.
The frequencies of responses in the two compartments differed, and 2/4 women that responded to epitopes in Nef 101-205 and Pol 601-710 showed responses in breast milk but no detectable responses in peripheral blood cells.

References

Sabbaj2002a Steffanie Sabbaj, Bradley H. Edwards, Mrinal K. Ghosh, Katherine Semrau, Sanford Cheelo, Donald M. Thea, Louise Kuhn, G. Douglas Ritter, Mark J. Mulligan, Paul A. Goepfert, and Grace M. Aldrovandi. Human Immunodeficiency Virus-Specific CD8(+) T Cells in Human Breast Milk. J. Virol., 76(15):7365-7373, Aug 2002. PubMed ID: 12097549. Show all entries for this paper.

Displaying record number 54357

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	B35-NQY9(RT)
Species (MHC/HLA)	human(B35)
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 55040

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location
Epitope	`NPDIVIYQY`	Epitope Alignment
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	binding affinity, immunodominance, optimal epitope

Notes

CTL responses were tested for both HIV-1 and EBV derived epitopes restricted by HLA-A, -B and -C alleles. HLA-B alleles more frequently induce detectable responses and that the responses are generally of greater magnitude than those for HLA-A and -C alleles.
The magnitude and frequency of CTL recognition were related to each other and that TCR avidity for HLA/peptide complexes is a more important determinant for magnitude of response than peptide binding affinity to HLA.
EBV response patterns were not significantly altered by HIV coinfection.
Epitope NPDIVIYQY elicited a magnitude of response of 180 SFC with a functional avidity of 0.0005nM and binding affinity of 9nM.

References

Bihl2006 Florian Bihl, Nicole Frahm, Loriana Di Giammarino, John Sidney, Mina John, Karina Yusim, Tonia Woodberry, Kaori Sango, Hannah S. Hewitt, Leah Henry, Caitlyn H. Linde, John V. Chisholm, III, Tauheed M. Zaman, Eunice Pae, Simon Mallal, Bruce D Walker, Alessandro Sette, Bette T. Korber, David Heckerman, and Christian Brander. Impact of HLA-B Alleles, Epitope Binding Affinity, Functional Avidity, and Viral Coinfection on the Immunodominance of Virus-Specific CTL Responses. J. Immunol., 176(7):4094-4101, 1 Apr 2006. PubMed ID: 16547245. Show all entries for this paper.

Displaying record number 56016

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	NY9(RT)
Subtype	B
Species (MHC/HLA)	human(B35)
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.
Previously described HLA-B35-restricted epitope NPDIVIYQY elicited an immune response in Chinese HIV-1 positive subjects as part of peptide RKQNPDIVIYQYMDDLYV. This epitope differs from another described epitope, HPDIVIYQY, at 1 residue, nPDIVIYQY.
5 of the 12 HLA-B35 carriers responded to NPDIVIYQY-containing peptide with average magnitude of CTL response of 662 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 457

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	( SF2)
Epitope	`NPDIVIYQY`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords	binding affinity, rate of progression, escape

Notes

HLA B35 is associated with rapid disease progression.
The sequences of 9 previously described HIV-1 B35 CTL epitopes were obtained in 10 HLA B35+ and 19 HLA B35- individuals.
3/9 CTL epitopes had substitutions that were more common in B35+ individuals than in B35- individuals -- only one of these reduced the binding of the peptide to B35 and was shown to be an escape mutation.
npEiviyqy was found in 8/10 of the B35+ individuals, and two of the B35- individuals---the D-->E substituted peptide had reduced binding affinity to B35 and may be an escape mutant.

References

Kawana1999 A. Kawana, H. Tomiyama, M. Takiguchi, T. Shioda, T. Nakamura, and A. Iwamoto. Accumulation of Specific Amino Acid Substitutions in HLA-B35-Restricted Human Immunodeficiency Virus Type 1 Cytotoxic T Lymphocyte Epitopes. AIDS Res. Hum. Retroviruses, 15:1099-1107, 1999. PubMed ID: 10461830. Show all entries for this paper.

Displaying record number 459

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT(328-336 IIIB)
Epitope	`NPDIVIYQY`	Epitope Alignment
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Binds HLA-B*3501.
CTL activity to this epitope was originally detected in a long-term survivor, however it has since been found in normal progressors -- it is cross-reactive with HIV-2 (HPDILIYQY), but D3E and V5I substitutions reduce binding Menendez-Arias1998

References

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

Shiga1996 H. Shiga, T. Shioda, H. Tomiyama, Y. Takamiya, S. Oka, S. Kimura, Y. Yamaguchi, T. Gojoubori, H. G. Rammensee, K. Miwa, and M. Takiguchi. Identification of Multiple HIV-1 Cytotoxic T Cell Epitopes Presented by Human Leukocyte Antigen B35 Molecule. AIDS, 10:1075-1083, 1996. PubMed ID: 8874623. Show all entries for this paper.

Displaying record number 461

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT(328-336 IIIB)
Epitope	`NPDIVIYQY`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords	review, escape

Notes

HIV IIIB proteins were used to define the range of CTL epitopes recognized by 3 lab workers accidentally infected with HIV-1 IIIB.
NPDIIIYQY, a variant found in HIV-1 JRCSF, was also recognized.
NPEIVIYQY, was also recognized.
NPDLVIYQY, was also recognized.
Menendez-Arias1998, in a review, notes that the YXDD motif, highly conserved among polymerases, overlaps this epitope -- CTL activity to this epitope was originally detected in a long-term survivor, however it has since been found in normal progressors -- it is cross-reactive with HIV-2 (HPDILIYQY), but D3E and V5I substitutions reduce binding.

References

Sipsas1997 N. V. Sipsas, S. A. Kalams, A. Trocha, S. He, W. A. Blattner, B. D. Walker, and R. P. Johnson. Identification of Type-Specific Cytotoxic T Lymphocyte Responses to Homologous Viral Proteins in Laboratory Workers Accidentally Infected with HIV-1. J. Clin. Invest., 99:752-762, 1997. To examine a situation where the autologous strain and the reference reagents would be the same, the CTL response of three lab workers accidentally infected with HIV IIIB was studied. Both group specific and type specific epitopes were targets for CTL clones. One subject had a broadening of CTL response over time, using a broad range of restricting HLA class I alleles. Characterization of the cytotoxic T lymphocyte (CTL) response against HIV-1 has been limited by the use of target cells expressing viral proteins from laboratory isolates of HIV-1. This approach has favored identification of group-specific CTL responses and precluded assessment of the extent of type-specific CTL responses directed against HIV-1. Using cells expressing viral proteins from the HIV-1 IIIB strain, we performed a detailed characterization of HIV-1-specific CTL response in three laboratory workers accidentally infected with HIV-1 IIIB. Eight of the epitopes identified were group specific, lying in relatively conserved regions of Gag, reverse transcriptase, and envelope. Three type-specific epitopes were identified, two of them in highly variable regions of envelope. In longitudinal studies in one subject, seven different epitopes and five different restricting HLA class I alleles were identified, with a progressive increase in the number of CTL epitopes recognized by this subject over time. Our data demonstrate that type-specific CTL responses make up a significant proportion of the host cellular immune response against HIV-1 and that a broadening of epitope specificity may occur. PubMed ID: 9045880. Show all entries for this paper.

Displaying record number 463

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT
Epitope	`NPDIVIYQY`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 exposed seronegative
Experimental methods
Keywords	review, subtype comparisons, HIV exposed persistently seronegative (HEPS)

Notes

A CTL response was found in exposed but uninfected prostitutes from Nairobi using previously-defined B clade epitopes that tended to be conserved in A and D clades -- such cross-reactivity could protect against both A and D and confer protection in Nairobi where both subtypes are circulating.
The A subtype consensus is HPDIVIYQY.
The D subtype consensus is NPEIVIYQY.
Menendez-Arias1998, in a review, notes that the YXDD motif, highly conserved among polymerases, overlaps this epitope -- CTL activity to this epitope was originally detected in a long-term survivor, however it has since been found in normal progressors -- it is cross-reactive with HIV-2 (HPDILIYQY), but D3E and V5I substitutions reduce binding.
Database note: First author "RowlandJones" is also found as "Rowland-Jones" on annotated papers in this database.

References

RowlandJones1998b S. Rowland-Jones, T. Dong, P. Krausa, J. Sutton, H. Newell, K. Ariyoshi, F. Gotch, S. Sabally, T. Corrah, J. Kimani, K. MacDonald, F. Plummer, J. Ndinya-Achola, H. Whittle, and A. McMichael. The Role of Cytotoxic T Cells in HIV Infection. Dev. Biol. Stand., 92:209-214, 1998. In this paper CTL response to previously defined conserved epitopes was found in exposed but uninfected prostitutes in Nairobi. Subtypes A and D are circulating in this regions, and the reactive epitopes tended to be conserved. Similarly previous studies in the Gambia showed that exposed but uninfected prostitutes tended to have B35 presented CTL epitopes conserved between HIV-1 and HIV-2. It was suggested that what was special about B35 is simply that it presents epitopes found both in HIV-1 and HIV-2. PubMed ID: 9554277. Show all entries for this paper.

Displaying record number 464

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	Pol( subtype B)
Epitope	`NPDIVIYQY`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 exposed seronegative
Experimental methods
Keywords	subtype comparisons

Notes

HIV-specific CTL were found in exposed seronegative prostitutes from Nairobi -- these CTL may confer protection.
Seroprevalence in this cohort is 90-95% and their HIV-1 exposure is among the highest in the world.
Most isolated HIV strains are clade A in Nairobi, although clades C and D are also found -- B clade epitopes are often cross-reactive, however stronger responses are frequently observed using A or D clade versions of epitopes.
Clade A version of epitope HPDIVIYQY, Clade D NPEIVIYQY.
Database note: First author "Rowland-Jones" is also found as "RowlandJones" on annotated papers in this database.

References

Rowland-Jones1998 S. L. Rowland-Jones, T. Dong, K. R. Fowke, J. Kimani, P. Krausa, H. Newell, T. Blanchard, K. Ariyoshi, J. Oyugi, E. Ngugi, J. Bwayo, K. S. MacDonald, A. J. McMichael, and F. A. Plummer. Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi. J. Clin. Invest., 102(9):1758-65, 1 Nov 1998. PubMed ID: 9802890. Show all entries for this paper.

Displaying record number 57924

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	Pol(330-338)
Epitope	`NPDIVIYQY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Patient MHC/HLA	A02:01, A24:02, B35:01, B35:03, C03:03, C04:01
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

The study tracked changes in amino acid residues across the whole genome over time during the first year of infection in 11 individuals representing 4 donor-recipient pairs and 3 independent seroconverters. 9 of the 11 individuals were enrolled during acute infection. In most cases, a single founder virus underwent selection, primarily in env and nef. Mutations were detected in the first week, and became consensus as early as 21 days post-onset of symptoms. Putative escape mutations were often rapidly replaced with mutually-exclusive mutations nearby. Escape mutations were more frequent than reversions.
Previously-documented B35-restricted epitope NPDIVIYQY was recognized by EliSpot assay in 1 HIV-positive B35-positive patient. The patient was negative at day 25, and positive by day 144 post-seroconversion.

References

Herbeck2011 Joshua T. Herbeck, Morgane Rolland, Yi Liu, Sherry McLaughlin, John McNevin, Hong Zhao, Kim Wong, Julia N. Stoddard, Dana Raugi, Stephanie Sorensen, Indira Genowati, Brian Birditt, Angela McKay, Kurt Diem, Brandon S. Maust, Wenjie Deng, Ann C. Collier, Joanne D. Stekler, M. Juliana McElrath, and James I. Mullins. Demographic Processes Affect HIV-1 Evolution in Primary Infection before the Onset of Selective Processes. J. Virol., 85(15):7523-7534, Aug 2011. PubMed ID: 21593162. Show all entries for this paper.

Displaying record number 57948

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT(175-183)
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	NY9
Subtype	A1, B, C
Species (MHC/HLA)	human(B35)
Immunogen	vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	vaccine-induced immune responses

Vaccine Details

Vaccine type	adenovirus
Vaccine strain	B clade HXB2, A clade 92RW020, C clade 97ZA012
Vaccine component	Env, Gag-Pol

Notes

The study evaluated vaccine-induced T-cell responses in 40 uninfected volunteers. 12 epitopes were targeted. Certain HLA alleles (B27, B57, B35, B14) were preferentially utilized, while other alleles (A02, B07) were rarely utilized. This preference was explained by 4 factors: higher affinity of specific peptides to specific HLAs, higher avidity of certain T-cell receptors, HLA and peptide interactions, and higher surface expression of certain HLAs.
5/7 B35-positive vaccinees responded to NPDIVIYQY. This epitope sequence is an exact match for 24% of M-clade and 66% of B-clade sequences in the LANL HIV sequence database.

References

Friedrich2011 David Friedrich, Emilie Jalbert, Warren L. Dinges, John Sidney, Alex Sette, Yunda Huang, M. Juliana McElrath, and Helen Horton. Vaccine-Induced HIV-Specific CD8+ T Cells Utilize Preferential HLA Alleles and Target-Specific Regions of HIV-1. J. Acquir. Immune Defic. Syndr., 58(3):248-252, 1 Nov 2011. PubMed ID: 21709567. Show all entries for this paper.

Displaying record number 52616

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT(175-183)
Epitope	`NPDIVIYQY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A23:01, B15:03, B*35:01, Cw2, Cw7
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	binding affinity, acute/early infection, early-expressed proteins

Notes

All proteins were scanned and optimal epitopes were mapped in a study of CD8+ INF-γ T-cell responses in 21 men within 15-92days post-HIV-1 infection. Subjects initially showed a narrow immune response with a mean of 2.3 epitopes recognized per patient. The immune response broadened later in infection. No correlation between the plasma viral load and the number of recognized epitopes or the frequency of IFN-γ secreting cells was observed, and there was no correlation between the functional avidity of a response and the abundance of IFNγ-secreting cells that recognized the epitope. The first epitopes to be recognized did not tend to be the most avid, and earliest responses tended to be directed against Nef, Tat, Vpr, and Env.
All HIV-1 proteins except Vpu were recognized, and responses to a total of 41 optimal epitopes were characterized; 24 had been identified previously. 48% of the total T-cell responses were directed against Nef and 43% were directed against Gag.
More common HLA alleles were less frequently used in primary infection than less common alleles, for example A3, B35, B57, and B62 were more frequently recognized than A1, A2, A30, and A44.

References

Cao2003 Jianhong Cao, John McNevin, Sarah Holte, Lisa Fink, Lawrence Corey, and M. Juliana McElrath. Comprehensive Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Secreting CD8+ T Cells in Primary HIV-1 Infection. J. Virol., 77(12):6867-6878, Jun 2003. PubMed ID: 12768006. Show all entries for this paper.

Displaying record number 61894

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT(330-338)
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	NY9
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Intracellular cytokine staining, Tetramer binding
Keywords	escape, HLA associated polymorphism

Notes

HLA-B*3501 is known to be a detrimental allele associated with rapid progression to AIDS. CTL responses to 16 known HLA-B*3501-restricted epitopes however, were studied in 63 B*3501+ ART-naive Japanese subjects, to find B*3501-epitope-specific CTLs which can suppress HIV-1 replication. The effect of viral protective-epitope mutations associated with B*3501 were also investigated and so one mechanism of the detrimental effect of HLA-B*3501 was clarified: the Y135F mutation within NefYF9, which is selected by HLA-A*2402-restricted CTL, impairs the ability of YF9-specific CTL to suppress HIV replication both in vivo and in vitro.
PolRT epitope NPDIVIYQY (NY9) elicited CTL response in 28/63 HLA-B*3501+ HIV-1-infected ART naive Japanese subjects, but no significant association was found with suppression of pVL (plasma viral load).

References

Murakoshi2018a Hayato Murakoshi, Madoka Koyanagi, Tomohiro Akahoshi, Takayuki Chikata, Nozomi Kuse, Hiroyuki Gatanaga, Sarah L. Rowland-Jones, Shinichi Oka, and Masafumi Takiguchi. Impact of a Single HLA-A*24:02-Associated Escape Mutation on the Detrimental Effect of HLA-B*35:01 in HIV-1 Control. EBioMedicine, 36:103-112, Oct 2018. PubMed ID: 30249546. Show all entries for this paper.

Displaying record number 460

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT(328-336 IIIB)
Epitope	`NPDIVIYQY`	Epitope Alignment
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

A CTL clone responsive to this epitope was obtained.
3/7 B35-positive individuals had a CTL response to this epitope.
D to E, or V to I, substitutions at positions 3 or 5, respectively, reduces CTL activity and binding to B*3501.

References

Tomiyama1997 H. Tomiyama, K. Miwa, H. Shiga, Y. I. Moore, S. Oka, A. Iwamoto, Y. Kaneko, and M. Takiguchi. Evidence of Presentation of Multiple HIV-1 Cytotoxic T Lymphocyte Epitopes by HLA-B*3501 Molecules That Are Associated with the Accelerated Progression of AIDS. J. Immunol., 158:5026-5034, 1997. PubMed ID: 9144523. Show all entries for this paper.

Displaying record number 61554

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT(175-183)
Epitope	`NPDIVIYQY`	Epitope Alignment
		Show epitope variants
Epitope Name	NY9
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	KI-833: B35:01; KI-929: B35:01; KI-980: B*35:01
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Intracellular cytokine staining
Keywords	subtype comparisons, variant cross-reactivity, mutation acquisition, drug resistance

Notes

Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-resistance mutations at Y181 in RT are known to overlap with 3 epitopes (IV10, IYQYMDDLYV; NY9, NPDIVIYQY or NPEIVIYQY; and KY9, KQNPDIVIY) in HIVs-B and -A/E. The effect of 3 different mutations, Y181I/V/C on recognition of the 3 epitopes across Subtype B and A/E viruses and in Japanese and Vietnamese populations was studied. Different effects of NNRTI-resistance RT181 mutations on CTL responses between the 2 subtype infections were demonstrated, particulary for NY9 .
Effects of Y181 mutations in the subtype B NY9 (NPDIVIYQY) epitope were found as Y181 mutants were recognized poorly by NY9-specific CTL or not recognized at all by clones generated from a subtype B-infected patient, because mutant NY9 peptides Y181V/C/I, had a slightly lower affinity to HLA-B*3501 than wt NY9.
Y181C mutation was not seen in Japanese treatment-naive subjects but was seen to accumulate in subtype A/E-infected Vietnamese NNRTI-naive subjects.
The NY9-3E subtype A/E epitope, NPEIVIYQY, elicited a response from NY9-specific CTL. NY9-3E-specific CTL cross-recognized all three of its mutant peptides - NY9-3E7I, NY9-3E7V, and NY9-3E7C.

References

Kuse2015 Nozomi Kuse, Mohammad Arif Rahman, Hayato Murakoshi, Giang Van Tran, Takayuki Chikata, Madoka Koyanagi, Kinh Van Nguyen, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi. Different Effects of Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations on Cytotoxic T Lymphocyte Recognition between HIV-1 Subtype B and Subtype A/E Infections. J. Virol., 89(14):7363-7372, Jul 2015. PubMed ID: 25972553. Show all entries for this paper.

Displaying record number 61869

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	NY9
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection, vaccine
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	vaccine-induced immune responses

Notes

The candidate tHIVconsvX vaccine is composed of 6 conserved Gag and Pol regions. Specific T cells - from 200 ART-naive, infected Japanese subjects previously exposed to the tHIVconsvX vaccine - that have the ability to supress HIV-1 replication were identified as recognizing 6 Pol epitopes. 6/25 epitopes (comprising 20 known and 5 novel mapped epitopes) remain associated with positive clinical outcome.
B*3501-restricted Pol epitope VPLDKDFRKY was found in 15-mer peptide pairs C254/255 and C256/257. While 12/221 Japanese subjects responded to the epitope, 4/20 HLA-carrying and 6/20 non-HLA carrying tested responders reacted to this epitope in EliSpot.

References

Zou2019 Chengcheng Zou, Hayato Murakoshi, Nozomi Kuse, Tomohiro Akahoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, Tomáš Hanke, and Masafumi Takiguchi. Effective Suppression of HIV-1 Replication by Cytotoxic T Lymphocytes Specific for Pol Epitopes in Conserved Mosaic Vaccine Immunogens. J. Virol., 93(7), 1 Apr 2019. PubMed ID: 30674626. Show all entries for this paper.

Displaying record number 58658

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	Pol(330-338)
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	RT NY9
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Country	Barbados, Botswana, Haiti, Japan, Mexico, South Africa, United Kingdom, United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons

Notes

While host HLA Class I genotype is the major genetic determinant of HIV-1 progression to AIDS, the same HLA allele could have varying outcomes for different infecting HIV clades. Overall, p24 Gag-specific epitopes were targeted significantly more frequently by C-clade-infected B*3501-positive subjects (55%) than B-clade-carrying B*3501-subjects (31%), while Env-specific epitopes were targeted more frequently by B-clade-infected subjects.
In general HLA-B*3501-restricted epitopes, were not targeted differentially for different clades. In contrast, CTL targeting against B*3501-restricted clade C Gag epitope, NPPIPVGDIY (NY10) but not clade B NY10, was associated with a lower viral set point and higher absolute CD4 count, i.e. better disease control. The above major result for epitope NY10 was confirmed for the B clade variant in Caucasian, Japanese and Mexican cohorts; C clade results were confirmed in South African (Durban) and Botswanan (Gaborne) cohorts.
In addition 5 new C-clade epitopes were identified.
B-clade specific epitope, RT NY9, NPDIVIYQY, elicited CTL response in >20% of B-clade infected subjects. The C-clade form of this epitope, NPeIVIYQY, was tested with cells from C-clade-infected subjects who responded to it.

References

Matthews2012 Philippa C. Matthews, Madoka Koyanagi, Henrik N. Kløverpris, Mikkel Harndahl, Anette Stryhn, Tomohiro Akahoshi, Hiroyuki Gatanaga, Shinichi Oka, Claudia Juarez Molina, Humberto Valenzuela Ponce, Santiago Avila Rios, David Cole, Jonathan Carlson, Rebecca P. Payne, Anthony Ogwu, Alfred Bere, Thumbi Ndung'u, Kamini Gounder, Fabian Chen, Lynn Riddell, Graz Luzzi, Roger Shapiro, Christian Brander, Bruce Walker, Andrew K. Sewell, Gustavo Reyes Teran, David Heckerman, Eric Hunter, Søren Buus, Masafumi Takiguchi, and Philip J. R. Goulder. Differential Clade-Specific HLA-B*3501 Association with HIV-1 Disease Outcome Is Linked to Immunogenicity of a Single Gag Epitope. J. Virol., 86(23):12643-12654, Dec 2012. PubMed ID: 22973023. Show all entries for this paper.

Displaying record number 52066

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT(175-183 IIIB)
Epitope	`NPDIVIYQY`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	epitope processing, escape

Notes

HIV polymorphisms in the RT protein were examined relation to HLA alleles found in a population of 473 participants in the Western Australian HIV Cohort Study. 64 significant associations between polymorphisms at particular positions and HLA alleles were detected, for HLA-B7, -B12, -B35 and -B15. Fifteen of these were in positions with known epitopes, 4 in anchor residues, 11 in other positions. Six additional polymorphic sites associated with particular HLA molecules flanked known epitopes and may relate to processing.
NPDIVIYQY was one of two epitopes characterized in detail. D177x substitutions are known to specifically abrogate binding to HLA-B*3501, and not other B*35 subtypes. D177x substitutions were associated with people who carried HLA-B*3501 and not other B*35 subtypes; considering high resolution typing generally strengthened the B*35 associations.

References

Moore2002b Corey B. Moore, Mina John, Ian R. James, Frank T. Christiansen, Campbell S. Witt, and Simon A. Mallal. Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science, 296(5572):1439-1443, 24 May 2002. PubMed ID: 12029127. Show all entries for this paper.

Displaying record number 1338

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	Pol(330-338)
Epitope	`NPDIVIYQY`	Epitope Alignment
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

CD8+ T-cells that bound one of six HIV-specific B*3501-epitope tetramers did not express CD28 or CD45A.
A significant increase in CD28-CD45RA- cells and a decrease of CD28+CD45RA+ cells was observed in chronically HIV-1-infected individuals relative to healthy individuals.
CD28-CD45RA- cells are likely to be effector cells and have high levels of perforin in their cytoplasm.
The mean percentage of total CD28- CD8+ cells in chronically infected HIV-1-infected patients was 76.6% in comparison to HIV-1-uninfected individuals (40.6%)

References

Tomiyama2000a H. Tomiyama, S. Oka, G. S. Ogg, S. Ida, A. J. McMichael, and M. Takiguchi. Expansion of HIV-1-specific CD28- CD45RA- CD8+ T cells in chronically HIV-1-infected individuals. AIDS, 14(13):2049-51, 8 Sep 2000. PubMed ID: 10997412. Show all entries for this paper.

Displaying record number 60025

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	Pol(330-338)
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	NQY9
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.
NPDIVIYQY had a significantly positive association with HLA B*3502,B*3503,B*5301; it was recognized by 17/37 B*3502,B*3503,B*5301-positive subjects and 6/304 B*3502,B*3503,B*5301-negative subjects.

References

Displaying record number 58081

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	Pol
Epitope	`NPDIVIYQY`	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 NPDIVIYQY.
Database note: the HLA restriction of this epitope in the database is B35. Both of the responders carried B35 alleles.

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.

Displaying record number 57316

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HXB2 Location	Pol(330-338) RT(175-183) DNA(3072..3098)	Pol Epitope Map
Author Location	RT
Epitope	`NPDIVIYQY`	Epitope Alignment
Epitope Name	NY9
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	United States
Experimental methods	Other
Keywords	dendritic cells

Notes

HLA-B*3503 (a B*35-Px molecule) is associated with rapid disease progression when compared with HLA-B*3501 (a B*35-Py molecule) even though they differ in structure by only one amino acid but both HLA bind identical epitopes. This phenomenon is found to be due to the significantly stronger binding of B*3503 to ILT4 (Immunoglobulin-like transcript 4, an inhibitory MHC Class I receptor found on monocytes and dendritic cells (DC)), which results in DC dysfunction.
NY9 was used as a B*35-binding epitope and was folded with the HLA molecule for ILT4-binding studies.

References

Huang2009a Jinghe Huang, James J. Goedert, Eric J. Sundberg, Thai Duong Hong Cung, Patrick S. Burke, Maureen P. Martin, Liliana Preiss, Jeffrey Lifson, Mathias Lichterfeld, Mary Carrington, and Xu G. Yu. HLA-B*35-Px-Mediated Acceleration of HIV-1 Infection by Increased Inhibitory Immunoregulatory Impulses. J. Exp. Med., 206(13):2959-2966, 21 Dec 2009. PubMed ID: 20008523. Show all entries for this paper.