Search CTL/CD8+ T-Cell Epitope Database

Found 22 matching records:

Displaying record number 60473

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	Pol(426-434)
Epitope	`YPGIKVRQL`	Epitope Alignment
Epitope Name	YL9
Species (MHC/HLA)	human(A*34)
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.
YPGIKVRQL had a significantly positive association with HLA A*34; it was recognized by 7/10 A*34-positive subjects and 22/196 A*34-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 60472

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	Pol(426-434)
Epitope	`YPGIKVRQL`	Epitope Alignment
Epitope Name	YL9
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.
YPGIKVRQL had a significantly positive association with HLA B*40; it was recognized by 14/24 B*40-positive subjects and 35/213 B*40-negative subjects.

References

Displaying record number 56394

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	RT(271-279)
Epitope	`YPGIKVRQL`	Epitope Alignment
Epitope Name	YL9
Subtype	B
Species (MHC/HLA)	human(B*42)
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*42-associated substitutions within optimally defined epitope YPGIKVRQL are at positions P2 and Q8, YpGIKVRqL.

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 59385

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	Pol(426-434)
Epitope	`YPGIKVRQL`	Epitope Alignment
		Show epitope variants
Subtype	C
Species (MHC/HLA)	human(B42, B81)
Immunogen	HIV-1 infection
Patient MHC/HLA	CH078: A01, A30, B42, B81, C17, C18
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	dynamics, escape, superinfection

Notes

CH078 was a South African patient dually infected with 2 subtype C strains. The patient's responses to epitopes were studied longitudinally for ˜441 days post-screening, and the responses and escape mutations were correlated to recombination between the 2 viral strains. Differential T cell targeting of the 2 founder viruses drove accelerated recombination-mediated escape.
Response to YPGIKVRQL was shared between both of the founder viruses and did not show escape. Restricting HLA B*42 was verified; B*81 was predicted based on binding motif but not experimentally verified.
YPGIKVRQL showed escape to YPGIrVRQL.

References

Ritchie2014 Adam John Ritchie, Fangping Cai, Nicola M. G. Smith, Sheri Chen, Hongshuo Song, Simon Brackenridge, Salim S. Abdool Karim, Bette T. Korber, Andrew J. McMichael, Feng Gao, and Nilu Goonetilleke. Recombination-Mediated Escape from Primary CD8+ T Cells in Acute HIV-1 Infection. Retrovirology, 11:69, 2014. PubMed ID: 25212771. Show all entries for this paper.

Displaying record number 55162

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location
Epitope	`YPGIKVRQL`	Epitope Alignment
Epitope Name	YL9 ?
Species (MHC/HLA)	human(B42)
Immunogen	HIV-1 infection
Country	South Africa, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	memory cells

Notes

Cohorts of HIV-infected subjects from the US and South Africa were screened for CD8+ EliSpot responses. Tetramer assays were performed for 13 frequently targeted HIV epitopes and compared to Flu, vaccinia, and EBV epitopes assayed in non-HIV-infected subjects. HIV tetramer+ CD8 T cells expressed less CD127, and this reduction was pervasive across all epitopes and alleles tested. These results indicated impaired HIV-specific memory CD8 T cell differentiation, regardless of level of control of viremia, epitopes targeted, or HLA alleles.

References

Wherry2006 E John Wherry, Cheryl L. Day, Rika Draenert, Joseph D. Miller, Photini Kiepiela, Tonia Woodberry, Christian Brander, Marylyn Addo, Paul Klenerman, Rafi Ahmed, and Bruce D. Walker. HIV-Specific CD8 T Cells Express Low Levels of IL-7Ralpha: Implications for HIV-Specific T Cell Memory. Virology, 353(2):366-373, 30 Sep 2006. PubMed ID: 16860834. Show all entries for this paper.

Displaying record number 492

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	RT(438-446 IIIB)
Epitope	`YPGIKVRQL`	Epitope Alignment
Species (MHC/HLA)	human(B42)
Immunogen	HIV-1 infection
Experimental methods
Keywords	responses in children, mother-to-infant transmission

Notes

YAGIKVRQL and YPGIKVKQL are naturally occurring variants that are both reactive.
YHKIKVRQL is a naturally occurring variant that has not been tested.
Epitope defined in the context of the Pediatric AIDS Foundation ARIEL Project, a mother-infant HIV transmission study.

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.

Walkerpercom1996 C. Wilson, B. Wilkes, D. Ruhl, and B. Walker. Personal communication, 1996. Defined in the context of the Pediatric AIDS Foundation ARIEL Project, a mother-infant HIV transmission study. Personal communication. Show all entries for this paper.

Displaying record number 493

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	Pol(438-446 IIIB)
Epitope	`YPGIKVRQL`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B42)
Immunogen	HIV-1 infection
Experimental methods
Keywords	mother-to-infant transmission, escape

Notes

This study describes maternal CTL responses in the context of mother-to-infant transmission.
Detection of CTL escape mutants in the mother was associated with transmission, but the CTL-susceptible forms of the virus tended to be found in infected infants.
An additional variant that gave a positive CTL response: YPGIKVKQL, YAGIKVRQL.
YHGIKVRQL was an escape mutant.

References

Wilson1999a C. C. Wilson, R. C. Brown, B. T. Korber, B. M. Wilkes, D. J. Ruhl, D. Sakamoto, K. Kunstman, K. Luzuriaga, I. C. Hanson, S. M. Widmayer, A. Wiznia, S. Clapp, A. J. Ammann, R. A. Koup, S. M. Wolinsky, and B. D. Walker. Frequent Detection of Escape from Cytotoxic T-Lymphocyte Recognition in Perinatal Human Immunodeficiency Virus (HIV) Type 1 Transmission: The Ariel Project for the Prevention of Transmission of HIV from Mother to Infant. J. Virol., 73:3975-3985, 1999. PubMed ID: 10196293. Show all entries for this paper.

Displaying record number 56492

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	RT
Epitope	`YPGIKVRQL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*42:01)
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).
YPGIKVRQL is a previously described HLA-B*4201-restricted epitope (part of Pol(RT) reacting peptide GKLNWASQIYpGIKVRQLCKL) that contains a B*4201-associated reversion at residue P (YpGIKVRQL).

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 1150

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	( LAI)
Epitope	`YPGIKVRQL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*42:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is a B*4201 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 53302

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	( C consensus)
Epitope	`YPGIKVRQL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*42:01)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	characterizing CD8+ T cells

Notes

HLA class I restricted CD8+ T-cell responses against HIV-1 were analyzed in African patients. Significantly more responses were shown to be HLA-B restricted. Viral load, CD4 count, and thus rate of disease progression were also associated with HLA-B alleles. In addition, the selection pressure imposed on HIV-1 by HLA-B alleles was shown to be substantially greater than by other alleles.
This epitope was suggested to be the epitope within a longer reactive peptide based on correspondence with a known epitope in the HIV database. Also, a significantly higher frequency of people in the Durban cohort who reacted with the peptide had this HLA type.

References

Kiepiela2004 Photini Kiepiela, Alasdair J. Leslie, Isobella Honeyborne, Danni Ramduth, Christina Thobakgale, Senica Chetty, Prinisha Rathnavalu, Corey Moore, Katja J. Pfafferott, Louise Hilton, Peter Zimbwa, Sarah Moore, Todd Allen, Christian Brander, Marylyn M. Addo, Marcus Altfeld, Ian James, Simon Mallal, Michael Bunce, Linda D. Barber, James Szinger, Cheryl Day, Paul Klenerman, James Mullins, Bette Korber, Hoosen M. Coovadia, Bruce D. Walker, and Philip J. R. Goulder. Dominant Influence of HLA-B in Mediating the Potential Co-Evolution of HIV and HLA. Nature, 432(7018):769-775, 9 Dec 2004. LA-UR 04-5920. PubMed ID: 15592417. Show all entries for this paper.

Displaying record number 54182

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	RT(271-279)
Epitope	`YPGIKVRQL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*42:01)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	HLA associated polymorphism

Notes

Publicly available HIV-1 subtype C sequences from South Africa and Botswana were analyzed, and 94 HLA-associated amino acid polymorphisms were found. Many polymorphisms were associated with multiple HLA allele classes. 12% associations were negative: association of virus expression of the consensus amino acid with a specific HLA allele. HLA-B alleles accounted for 50% of associations. 19 HLA-associated polymorphisms were embedded in previously defined epitopes.
YPGIKVRQL was a previously defined B*4201 presented epitope that encompassed an B*42 associated polymorphism, YpGIKVRQL, in the second position. This epitope was found embedded in a previously determined immunoreactive region.

References

Boutwell2007 Christian L. Boutwell and M. Essex. Identification of HLA Class I-Associated Amino Acid Polymorphisms in the HIV-1C Proteome. AIDS Res. Hum. Retroviruses, 23(1):165-174, Jan 2007. PubMed ID: 17263647. Show all entries for this paper.

Displaying record number 56259

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location
Epitope	`YPGIKVRQL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*42:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A23:01, A29:02, B41:01, B42:01, C*17:01
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	rate of progression

Notes

47 HIV-1 subtype C infected patients were followed longitudinally to determine whether there was a relation between magnitude and breadth of CTL responses in primary, acute infection (measured by IFN-gamma ELISpot) and disease progression (measured as viral load at 12 months). CTL responses to Nef were dominant (targeting 6 epitopic regions), followed by responses to Gag, Pol, Rev, Vpr, Env, Vpu, Vif and finally Tat.
Known epitope YPGIKVRQL is HLA-B*4201-restricted. Response to a peptide containing this epitope was detected in a rapid progressor 12 weeks post-infection.

References

Gray2009 Clive M. Gray, Mandla Mlotshwa, Catherine Riou, Tiyani Mathebula, Debra de Assis Rosa, Tumelo Mashishi, Cathal Seoighe, Nobubelo Ngandu, Francois van Loggerenberg, Lynn Morris, Koleka Mlisana, Carolyn Williamson, Salim Abdool Karim, and CAPRISA 002 Acute Infection Study Team. Human Immunodeficiency Virus-Specific gamma Interferon Enzyme-Linked Immunospot Assay Responses Targeting Specific Regions of the Proteome during Primary Subtype C Infection Are Poor Predictors of the Course of Viremia and Set Point. J. Virol., 83(1):470-478, Jan 2009. PubMed ID: 18945774. Show all entries for this paper.

Displaying record number 59435

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	Pol(426-434)
Epitope	`YPGIKVRQL`	Epitope Alignment
		Show epitope variants
Epitope Name	RT-YL9
Subtype	C
Species (MHC/HLA)	human(B*42:01)
Immunogen	HIV-1 infection
Country	Botswana, South Africa, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Other, Tetramer binding
Keywords	immunodominance, escape

Notes

2,093 HLA-B*4201⁺ ART-naive female adults from 5 cohorts with chronic C-clade infection were studied to determine factors controlling immunodominance. Immunodominant hierarchy of response observed across 20 HLA-B*4201-restricted epitopes was not linked to peptide-B*4201 binding affinity or stability. Immunodominance correlated instead with the particular amino acid residues within (TCRβ) TRB sequences. Extreme TCR biases towards generating identical or 'public' epitope-specific TCRs in multiple individuals therefore were statistically the greatest influence upon Immunodomination.
13 B*4201⁺-restricted novel epitopes were identified by EliSpot screening of 181 females with 410 HIV-1 OLPs.
11 different public clonotypes were identified and were used by the top 3 ranked immunodominant epitope-specificities.
6/10 most immunodominant epitopes were Gag/Pol/Vpr-specific and 100% showed selection pressure on HIV. Of 4 epitopes that were Nef/Vif-specific and among most immunodominant, only 25% i.e one epitope experienced selection pressure in the virus.
Epitope YPGIKVRQL from OLP RT-202 (SKLNWASQIYPGIKVRQL) had a targeting frequency of ˜16% of 154 HLA-B*4201⁺ subjects. Immunodominance rank was 10/20 tested epitopes.
RT-YL9-HLA-B*4202's binding affinity, K_d = 3 nM; stability, K_1/2 = 6.2h.
6 polymorphisms were selected by HLA-B*4201 in this RT-YL9 epitope, P427S, P427A, P427Q, I429V, Q433N and K436R.

References

Kloverpris2015 Henrik N Kløverpris, Reuben McGregor, James E. McLaren, Kristin Ladell, Mikkel Harndahl, Anette Stryhn, Jonathan M. Carlson, Catherine Koofhethile, Bram Gerritsen, Can Keşmir, Fabian Chen, Lynn Riddell, Graz Luzzi, Alasdair Leslie, Bruce D. Walker, Thumbi Ndung'u, Søren Buus, David A. Price, and Philip J. Goulder. CD8+ TCR Bias and Immunodominance in HIV-1 Infection. J. Immunol., 194(11):5329-5345, 1 Jun 2015. PubMed ID: 25911754. Show all entries for this paper.

Displaying record number 58723

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	RT(271-278)
Epitope	`YPGIKVRQL`	Epitope Alignment
		Show epitope variants
Epitope Name	RT-YL9
Subtype	C
Species (MHC/HLA)	human(B42:01, B42:02)
Immunogen	HIV-1 infection
Patient MHC/HLA	A30:01, B42:02, C17:01; A30:01, B42:01, C17:01
Country	Botswana, South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Tetramer binding
Keywords	escape, HLA associated polymorphism, novel epitope

Notes

Using an outbred cohort of 2,093 clade-C-infected southern African subjects who carry the HLA-B*42 allele, the authors determine that a single amino acid change between B*4202 and B*4201 is responsible for the difference in HLA-B*4201 presenting multiple Gag epitopes with a lower VL; and HLA-B*0402 which presents no p24 Gag epitopes. Thus a single nucleotide polymorphism (SNP) on the HLA class I locus is associated with significant differences in HIV disease control.
While no substantial difference was seen in the peptide binding motifs of both HLAs, as well as no overall difference in targeting of Pol, Nef or Env epitopes, a significantly larger number of HLA-B*4201-positive subjects recognized Gag epitopes.
RT epitope YL9, YPGIKVRQL, was recognized by ˜70% B*4202-positive responding subjects versus ˜20% of HLA-B*4201 carriers, but B*4201 has a longer half life of binding YL9 than B*4202 does. It is a novel C-clade epitope restricted by HLA-B*4202.
RT-YL9 mutations are at positions 2,3,5,7,8 - YaGIKVRQL, YPGIrVRQL, YPGIKVRgL, YPGIKVRrL, YPGIKVkkL, YqGIKVRQL, YPkIKVRQL, YPGIKVsQL and other mutations. Almost 100% of B*4201- and B*4202-subjects carried an escape mutation while only 50% of non-B*42 carriers did.

References

Kloverpris2012a Henrik N. Kløverpris, Mikkel Harndahl, Alasdair J. Leslie, Jonathan M. Carlson, Nasreen Ismail, Mary van der Stok, Kuan-Hsiang Gary Huang, Fabian Chen, Lynn Riddell, Dewald Steyn, Dominique Goedhals, Cloete van Vuuren, John Frater, Bruce D. Walker, Mary Carrington, Thumbi Ndung'u, Søren Buus, and Philip Goulder. HIV Control through a Single Nucleotide on the HLA-B Locus. J. Virol., 86(21):11493-11500, Nov 2012. PubMed ID: 22896606. Show all entries for this paper.

Displaying record number 60475

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	Pol(426-434)
Epitope	`YPGIKVRQL`	Epitope Alignment
Epitope Name	YL9
Species (MHC/HLA)	human(B*57)
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.
YPGIKVRQL had a significantly positive association with HLA B*57; it was recognized by 41/104 B*57-positive subjects and 49/237 B*57-negative subjects.

References

Displaying record number 60476

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	Pol(426-434)
Epitope	`YPGIKVRQL`	Epitope Alignment
Epitope Name	YL9
Species (MHC/HLA)	human(B*58:01)
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.
YPGIKVRQL had a significantly positive association with HLA B*5801; it was recognized by 4/8 B*5801-positive subjects and 18/188 B*5801-negative subjects.

References

Displaying record number 60474

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	Pol(426-434)
Epitope	`YPGIKVRQL`	Epitope Alignment
Epitope Name	YL9
Species (MHC/HLA)	human(B*81)
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.
YPGIKVRQL had a significantly positive association with HLA B*81; it was recognized by 6/7 B*81-positive subjects and 29/206 B*81-negative subjects.

References

Displaying record number 56151

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	RT
Epitope	`YPGIKVRQL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Experimental methods
Keywords	HLA associated polymorphism

Notes

3 phylogenetic correction methods---MLL (maximum likelihood character state analysis followed by likelihood ratio test), MLF (maximum likelihood character state analysis followed by Fisher test), and parsimony character state analysis were used to identify points in the HIV-1 subtype C proteome that conferred susceptibility or resistance to CTLs. Associations of HLA-epitope combinations that were inferred to be susceptible or resistant were organized into immunological sets that would help identify the best residues and genes as candidates for vaccines. While all proteins were interrogated, Gag, Pol, Env and Nef were focused upon. Amino acid changes were evaluated for association with plasma viral load.
Proteome maps may be seen at http://www.hiv.lanl.gov/content/immunology/hlatem/study5/index.html with information showing single or multiple sites involving escape and reversion.
HLA- B and -C alleles associated more with aa changes than HLA-A, suggesting that the former two are more important in driving viral evolution.
The ratio of susceptible to resistant residues in HIV proteins was in descending order, Vpr>Gag>Rev>Pol>Nef>Vif>Tat>Env>Vpu, showing that epitopes from the earlier proteins are more conserved owing to viral fitness cost upon mutation.
This Pol HLA-B*42-restricted epitope, YPGIKVRQL, lies within a set of 6 immunological associations, experiencing conflicting selective pressures.

References

Rousseau2008 Christine M. Rousseau, Marcus G. Daniels, Jonathan M. Carlson, Carl Kadie, Hayley Crawford, Andrew Prendergast, Philippa Matthews, Rebecca Payne, Morgane Rolland, Dana N. Raugi, Brandon S. Maust, Gerald H. Learn, David C. Nickle, Hoosen Coovadia, Thumbi Ndung'u, Nicole Frahm, Christian Brander, Bruce D. Walker, Philip J. R. Goulder, Tanmoy Bhattacharya, David E. Heckerman, Bette T. Korber, and James I. Mullins. HLA Class I-Driven Evolution of Human Immunodeficiency Virus Type 1 Subtype C Proteome: Immune Escape and Viral Load. J. Virol., 82(13):6434-6446, Jul 2008. PubMed ID: 18434400. Show all entries for this paper.

Displaying record number 54199

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	RT(271-279)
Epitope	`YPGIKVRQL`	Epitope Alignment
Epitope Name	YL9
Subtype	C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Other, Tetramer binding
Keywords	supertype, HLA cross-presentation, TCR usage, HLA associated polymorphism

Notes

14 promiscuous HIV-specific CTL epitopes presented by B7 supertype alleles were described. It was shown that CTLs targeting an identical epitope that are restricted by closely related but different HLA alelles differ in several ways: by occurrence of distinct HLA-specific escape mutations, by recruitment of distinct TCRs by peptide/MHC complexes, and by functional avidity of CTLs. Since there were no differences in the frequency, magnitude or immunodominance of the CTL responses restricted by different HLA alleles, it is suggested that the unique peptide/MHC complexes generated by closely related HLA induce qualitatively different CTL responses.
Statistically significant associations between numbers of HLA-4201 expressing subjects and epitope YPGIKVRQL were found.
A strong association between B*4201 and variation in epitope YL9 was found.

References

Leslie2006 Alasdair Leslie, David A. Price, Pamela Mkhize, Karen Bishop, Almas Rathod, Cheryl Day, Hayley Crawford, Isobella Honeyborne, Tedi E. Asher, Graz Luzzi, Anne Edwards, Christine M. Rousseau, James I. Mullins, Gareth Tudor-Williams, Vas Novelli, Christian Brander, Daniel C. Douek, Photini Kiepiela, Bruce D. Walker, and Philip J. R. Goulder. Differential Selection Pressure Exerted on HIV by CTL Targeting Identical Epitopes but Restricted by Distinct HLA Alleles from the Same HLA Supertype. J. Immunol., 177(7):4699-4708, 1 Oct 2006. PubMed ID: 16982909. Show all entries for this paper.

Displaying record number 54953

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location
Epitope	`YPGIKVRQL`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection, vaccine
Patient MHC/HLA	203-157: A30:01, A30:02, B42, B44
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	vaccine-induced immune responses, acute/early infection

Vaccine Details

Vaccine type	canarypox prime with gp120 boost, polyepitope
Vaccine strain	B clade LAI, B clade MN
Vaccine component	Gag, gp120, gp41, Nef, Pol, Protease

Notes

T cell responses during early infection in individuals previously enrolled in HIV vaccine trials were compared with those of nonvaccinated subjects.
None of the breakthrough infections possessed vaccine-induced T-cell responses preinfection and 85-86% of vaccinees and nonvaccinees with primary infection developed T-cell responses postinfection, indicating that vaccinees' ability to mount T-cell response postinfection is not compromized by previous immunization.
Breakthrough subjects recognized 43 T-cell epitopes, 8 of them novel, and 25% were present in the vaccine.
This epitope was not contained in the vaccine, but the linked vaccinated patient in whom the study was conducted recognized it after developing infection.

References

Horton2006a Helen Horton, Colin Havenar-Daughton, Deborah Lee, Erin Moore, Jianhong Cao, John McNevin, Thomas Andrus, Haiying Zhu, Abbe Rubin, Tuofu Zhu, Connie Celum, and M. Juliana McElrath. Induction of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Responses in HIV Vaccine Trial Participants Who Subsequently Acquire HIV-1 Infection. J. Virol., 80(19):9779-9788, Oct 2006. PubMed ID: 16973582. Show all entries for this paper.

Displaying record number 62844

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HXB2 Location	Pol(426-434) RT(271-279) DNA(3360..3386)	Pol Epitope Map
Author Location	RT(271-279)
Epitope	`YPGIKVRQL`	Epitope Alignment
Epitope Name	YL9
Subtype	B, C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection, engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	acute/early infection, HLA associated polymorphism, chronic infection, protective allele

Notes

The in vitro replicative capacity (RC) of recombinant subtype B NL4-3 viruses expressing subtype C RT-integrase sequences derived from recently infected patients correlated positively with log subsequent VL set point and a higher rate of CD4 decline, while the RC of NL4-3 recombinants expressing subtype C RT-integrase sequences derived from chronically infected patients correlated positively with log VL but negatively with CD4 count. Protective & risk HLA alleles were associated with lower and higher RC values, respectively, and the number of HLA-associated polymorphisms in RT correlated positively with RC while the inverse was observed for integrase. About 90% of RT-integrase polymorphisms significantly associated with altered RC occurred inside or within 5 aa of A-list epitopes (LANL HIV Database).
RT polymorphism P272K and subtype C consensus P272 were associated with altered RC and are within well-defined epitope YPGIKVRQL, YL9, known to bind to B*42:01. Residue 272 is also located within overlappping epitope QIYPGIKVR.
Rare P272K occurred in 5 participant-derived recombinant viruses with a substantially reduced median RC of 0.84, while 350 analogous viruses with consensus P272 had a median RC of 0.93, relative to unmodified NL4-3. Authors suggest P272K may be a novel fitness-costly immune-driven escape mutation.

References

Ojwach2018 Doty B. A. Ojwach, Daniel MacMillan, Tarylee Reddy, Vladimir Novitsky, Zabrina L. Brumme, Mark A. Brockman, Thumbi Ndung'u, and Jaclyn K. Mann. Pol-Driven Replicative Capacity Impacts Disease Progression in HIV-1 Subtype C Infection. J. Virol., 92(19), 1 Oct 2018. PubMed ID: 29997209. Show all entries for this paper.

Displaying record number 62880

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HXB2 Location	Pol(426-434) RT(271-279)	Pol Epitope Map
Author Location	RT(271-279)
Epitope	`YPGIKVRQL`	Epitope Alignment
		Show epitope variants
Epitope Name	YL9
Subtype	B, C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection, engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	vaccine antigen design

Notes

Single nucleotide mutations were introduced onto a patient-derived subtype C reverse transciptase (RT)-integrase sequence (SK-278, 98.2% similar to Con C) on a subtype B NL4-3ΔRT-integrase backbone and assessed for their impact on <i>in vitro</i> viral replicative capacity (RC) in a GFP-based assay. Structural modeling of the RT mutations that mediated the greatest RC reductions (A158S, V241I, & I257V) provided insight into functional consequences.
Relative to NL4-3 recombinant virus encoding wild-type SK-278 RT-integrase, the introduction of RT mutation P272K mediated ˜11% reduction in RC while the introduction of P272A did not mediate a significant reduction in RC.
Residue 272 is located within best-defined epitope YPGIKVRQL (YL9, known to bind to B*42:01, B*57, & B*81), as well as overlapping epitope QIYPGIKVR, which are both present in SK-278.

References

Ojwach2021 Doty B. A. Ojwach, Paradise Madlala, Michelle Gordon, Thumbi Ndung'u, and Jaclyn K. Mann. Vulnerable targets in HIV-1 Pol for attenuation-based vaccine design. Virology, 554:1-8 doi, Feb 2021. PubMed ID: 33316731 Show all entries for this paper.