Search CTL/CD8+ T-Cell Epitope Database

Found 17 matching records:

Displaying record number 54290

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef
Epitope	`KAAFDLSFF`	Epitope Alignment
Epitope Name	KF9
Subtype	C
Species (MHC/HLA)	human(B57, B58:01)
Immunogen	HIV-1 infection
Country	Botswana, Ethiopia, South Africa, Tanzania
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, HLA associated polymorphism

Notes

Host HLA associated mutational patterns in HIV can be a consequence of immune escape, but to cleanly resolve whether or not such patterns are the result of lineage effects or immune pressure, it is helpful to incorporate the phylogenetic history of the virus into the test statistics. Most of the HLA associations that appeared to result from immune escape in an earlier study (Moore et al., Science 296:1439 2002) were found to be a consequence of the phylogenetic history of the virus, not immune escape. Other HLA associations were validated, and some additional HLA-associated mutations were identified through incorporating the viral phylogenetic tree in the analysis.
There are two variant forms of this B57/B5801 epitope at the second position KaAFDLSFF and KgAFDLSFF. Leslie et al., J Exp Med. 2005 201:891 suggest that the escape form KgAFDLSFF may have come to dominate the C clade lineage over time due to higher HLA B57/B5801 frequencies in southern Africa. Bhattacharya suggests lineage effects are also playing an important role in the observed amino acid frequencies, and note that the ratio of G/A has not change over time, and that the frequency of G/A in different epidemic populations does not correlate with HLA B57/B5801 allele frequency.

References

Bhattacharya2007 Tanmoy Bhattacharya, Marcus Daniels, David Heckerman, Brian Foley, Nicole Frahm, Carl Kadie, Jonathan Carlson, Karina Yusim, Ben McMahon, Brian Gaschen, Simon Mallal, James I. Mullins, David C. Nickle, Joshua Herbeck, Christine Rousseau, Gerald H. Learn, Toshiyuki Miura, Christian Brander, Bruce Walker, and Bette Korber. Founder Effects in the Assessment of HIV Polymorphisms and HLA Allele Associations. Science, 315(5818):1583-1586, 16 Mar 2007. PubMed ID: 17363674. Show all entries for this paper.

Displaying record number 58635

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef(82-90)
Epitope	`KAAFDLSFF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF9
Subtype	C
Species (MHC/HLA)	human(B57, B58:01)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, HLA binding
Keywords	subtype comparisons, computational epitope prediction, mother-to-infant transmission, escape, viral fitness and reversion, optimal epitope

Notes

The authors correlate preservation of certain consensus epitope sequences with HLA-I (novel epitope KF9, KAAFDLSFF or KAAVDLSHF, with B*57/5801; and LI9, LPPVVAKEI, with B*51) as opposed to the usual correlation between variants from the consensus and HLA-I.
KAAFDLSFF is the susceptible C-clade optimal form of the KF9 epitope, and KgAFDLSFF an escape variant.

References

Leslie2005a Alasdair Leslie, Daniel Kavanagh, Isobella Honeyborne, Katja Pfafferott, Charles Edwards, Tilly Pillay, Louise Hilton, Christina Thobakgale, Danni Ramduth, Rika Draenert, Sylvie Le Gall, Graz Luzzi, Anne Edwards, Christian Brander, Andrew K. Sewell, Sarah Moore, James Mullins, Corey Moore, Simon Mallal, Nina Bhardwaj, Karina Yusim, Rodney Phillips, Paul Klenerman, Bette Korber, Photini Kiepiela, Bruce Walker, and Philip Goulder. Transmission and Accumulation of CTL Escape Variants Drive Negative Associations between HIV Polymorphisms and HLA. J. Exp. Med., 201(6):891-902, 21 Mar 2005. PubMed ID: 15781581. Show all entries for this paper.

Displaying record number 53263

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef( C consensus)
Epitope	`KAAFDLSFF`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, viral fitness and reversion

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.
People who carried B57 all carried a variant of this epitope, while about half of the people who did not carry B57 carried the susceptible form, suggesting there is not a high fitness cost and revision rate in this case.
HLA-B57 was associated with a low viral load.

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 53831

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef(82-90)
Epitope	`KAAFDLSFF`	Epitope Alignment
		Show epitope variants
Subtype	C
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Patient MHC/HLA	A30:01, A66, B42:01, B58:02, C06:02, C17:01; A66, A68, B57, B58:02, C06:02, C07:01
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	responses in children, mother-to-infant transmission, escape, acute/early infection

Notes

HIV-specific CTLs in infants were shown to be able to select for viral escape variants early in life, despite a lack of escape with the same CTL specificity in the mother. Infant CTL responses may be compromised by transmission of escape variants that arose in the mother and also those that arose in the father, if the father was the source of the mother's infection.
KAAFDLSFF is the C consensus form of the epitope; the autologous form in the mother was KAAFDLgFF, and this was transmitted to her infant. By 33 weeks a new dominant form of the epitope had emerged in the infant: gAAFDLgFF.

References

Pillay2005 Thillagavathie Pillay, Hua-Tang Zhang, Jan W. Drijfhout, Nicola Robinson, Helen Brown, Munira Khan, Jagadesa Moodley, Miriam Adhikari, Katja Pfafferott, Margaret E. Feeney, Anne St. John, Edward C. Holmes, Hoosen M. Coovadia, Paul Klenerman, Philip J. R. Goulder, and Rodney E. Phillips. Unique Acquisition of Cytotoxic T-Lymphocyte Escape Mutants in Infant Human Immunodeficiency Virus Type 1 Infection. J. Virol., 79(18):12100-12105, Sep 2005. PubMed ID: 16140787. Show all entries for this paper.

Displaying record number 56603

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef(82-90)
Epitope	`KAAFDLSFF`	Epitope Alignment
Epitope Name	KF9
Subtype	C
Species (MHC/HLA)	human(B*58:01, B57)
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-B57/*5801-restricted KAAFDLSFF (KF9) was associated with a polymorphism at K(A)AFDLSFF.

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 61671

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef(82-90)
Epitope	`KAAFDLSFF`	Epitope Alignment
Epitope Name	KF9
Species (MHC/HLA)	human(B*57:01)
Immunogen	peptide-HLA interaction
Experimental methods	Other, Tetramer binding
Keywords	structure, NK cells, protective allele

Notes

A structure-driven approach to characterize specific peptide preferences of protective HLA-B*5701-restricted epitopes of HIV-1 with NK cell receptors is used in this study. In addition, HLA-Bw4-restricted epitope ligands recognized by KIR3DS1 were identified, showing direct interaction between these molecules resulting in NK cell activation.
C-terminal epitope residues are known to affect KIR3DL1 recognition so that replacing position 8 of the human peptide LF9, LSSPVTKSF, with glutamate (E) i.e. LSSPVTKeF dramatically reduces binding and this is possibly due to side chain protrusion of E that would clash with E282 of the KIR D2 domain. And replacing that position with alanine (A) might disallow contact with L166 of the KIR D1 domain, abolishing peptide-KIR3DL1*001 interaction.
Allotype-specific differences were seen in binding to KIR3DS1 as compared to KIR3DL1, specifically at amino acids W138, S163, R166 and L199 (not found in KIR3DL1). W138, S163, R166 strongly inhibit binding of KIR3DL1*001 to HLA-A*2402; but only R166 impairs binding of KIR3DL1*001 to HLA-B*5701.
Peptide-specific effects also modulate binding sensitivity of R166-KIR3DS1-like mutants and KIR3DS1 (which contains R166). HIV-Nef KF9, KAAFDLSFF, presented by HLA-B*5701 is bound by KIR3DS1. Position 8F (or 8W) containing peptides were tested to see if they could induce binding of KIR3DS1 to HLA-B*5701, and HIV peptide KF9 was 1 of 2 which did.

References

OConnor2015 Geraldine M. O'Connor, Julian P. Vivian, Emma Gostick, Phillip Pymm, Bernard A. P. Lafont, David A. Price, Jamie Rossjohn, Andrew G. Brooks, and Daniel W. McVicar. Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1. J. Virol., 89(10):5213-5221, May 2015. PubMed ID: 25740999. Show all entries for this paper.

Displaying record number 56224

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location
Epitope	`KAAFDLSFF`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B57:01, B58:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A03:01, A23:01, B15:03, B58:02, C02:10, C06:02
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.
KAAFDLSFF is a known HLA-B5701 and -B5801-restricted epitope that is part of peptide RPMTYKAAFDLSFFLKEKG which elicited responses in 9/25 patients, and which belongs to peptide pool 3 that accounted for over 70% of Nef responses. Response to a peptide containing this epitope was detected in 1 rapid progressor at 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 58821

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef(81-89)
Epitope	`KAAFDLSFF`	Epitope Alignment
Epitope Name	KF9 Nef
Subtype	C
Species (MHC/HLA)	human(B57:02, B57:03, B*58:01)
Immunogen	HIV-1 infection
Country	Botswana, South Africa, Zimbabwe
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Intracellular cytokine staining, Tetramer binding
Keywords	optimal epitope, HLA associated polymorphism, novel epitope

Notes

1,010-HIV C clade-chronically infected subjects were tested in order to distinguish levels of immune control by related but different HLA-B*57/58. B*57 micropolymorphisms (B*5703 and B*5702) as well as B*5801 have differing CTL specificity and also present different p24 Gag epitopes. This results in different immune selection pressures on the HIV-C virus.
Though all three studied HLA alleles, B*5801, B*5702 and B*5703 are significantly associated with lower viral-load (VL) set points, HLA-B*5703, followed closely by B*5702 is the most potent controller with lowest VL and HLA-B*5702, followed by B*5703 and then B*5801 are associated with highest CD4 counts.
By using 410 overlapping 18-mers that span the HIV-C proteome in EliSpot assays, 17 epitopes were identified that are presented by one of HLAs-B*5801/5702/5703, 13 of them novel.
Novel epitope KF9 Nef, KAAFDLSFF, was confirmed to be optimal by peptide truncation using B*5703-restricted CTL from chronically infected subject N102.
The binding affinity and stability of KF9 is greatest to B*5702; ˜45% B*5702-responders recognized KF9, >20% B*5703- and B*5801-responders recognized KF9 Nef.
Almost 100% B*5702- and B*5703-positive subjects carried mutations in KF9. ˜90% B*5801-positive subjects and ˜60% non-B*57 subjects sustained KF9 variations.

References

Kloverpris2012 Henrik N. Kloverpris, Anette Stryhn, Mikkel Harndahl, Mary van der Stok, Rebecca P. Payne, Philippa C. Matthews, Fabian Chen, Lynn Riddell, Bruce D. Walker, Thumbi Ndung'u, Søren Buus, and Philip Goulder. HLA-B*57 Micropolymorphism Shapes HLA Allele-Specific Epitope Immunogenicity, Selection Pressure, and HIV Immune Control. J. Virol., 86(2):919-929, Jan 2012. PubMed ID: 22090105. Show all entries for this paper.

Displaying record number 61217

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef
Epitope	`KAAFDLSFF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF9
Subtype	B
Species (MHC/HLA)	human(B57:02, B57:03, B*58:01)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	review, escape, HLA associated polymorphism

Notes

This review follows protective HLA-I molecules and their conserved p24 Gag epitopes that escape with a fitness cost to viral replicative capacity (VRC). Compensatory viral mutations can correct for VRC loss to different extents. This results in protective HLA losing impact as well as a modest decline in virulence of HIV with reduced VRC.
Epitope KAAFDLSFF is restricted by strongly protective alleles. An escape is found at A83G. In Clade C the variant is the dominant dominant circulating form found.

References

Kloverpris2015a Henrik N. Kløverpris, Alasdair Leslie, and Philip Goulder. Role of HLA Adaptation in HIV Evolution. Front. Immunol., 6:665, 18 Jan 2016. PubMed ID: 26834742. Show all entries for this paper.

Displaying record number 58648

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location
Epitope	`KAAFDLSFF`	Epitope Alignment
Species (MHC/HLA)	human(B*57:03)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander noted this as an optimal B*5703 epitope based on data from Leslie2005a and Kloverpris2012.

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 62176

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef(82-90 NL4-3, SK68)
Epitope	`KAAFDLSFF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF9
Subtype	B
Species (MHC/HLA)	human(B*58:01)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	subtype comparisons, Nef-mediated down-regulation

Notes

Subtype-specific Nef mutations at 20M/I and 88S/G for clades B/C HIV-1 contribute to functional differences seen in an increase in HLA-I downregulation by subtype B. Escape S88G is associated with a significant cost.
S88G is an escape variant selected by CTL responses targeting the HLA-B*58:01-restricted KF9 epitope, KAAFDLSFF. KAAFDLgFF, found in subtype C downregulates the loss of cell surface HLA-I and CD4.

References

Mann2015 Jaclyn K. Mann, Saleha Omarjee, Phumzile Khumalo, and Thumbi Ndung'u. Genetic Determinants of Nef-Mediated CD4 and HLA Class I Down-Regulation Differences between HIV-1 Subtypes B and C. Virol. J., 12:200, 25 Nov 2015. PubMed ID: 26607225. Show all entries for this paper.

Displaying record number 57753

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef
Epitope	`KAAFDLSFF`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*58:01)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, acute/early infection

Notes

Immunological responses in early subtype C infection were characterized. Nef, Pol and Gag were the most frequently targeted proteins from as early as 3 to 8 weeks postinfection. Nef was immunodominant, with more than 75% of individuals recognizing Nef. Many responses to peptide pools were derived from the recognition of one immunodominant peptide.
Two B*5801-positive acutely HIV-1-infected individuals had a peptide response to presumed optimal epitope KAAFDLSFF within peptide RPMTYKAAFDLSFFLKEKG. For one patient, autologous viral escape occurred in 17.5 weeks, and response was lost at 19 weeks. For the other patient, there was no evidence of escape.

References

Mlotshwa2010 Mandla Mlotshwa, Catherine Riou, Denis Chopera, Debra de Assis Rosa, Roman Ntale, Florette Treunicht, Zenda Woodman, Lise Werner, Francois van Loggerenberg, Koleka Mlisana, Salim Abdool Karim, Carolyn Williamson, Clive M Gray, and CAPRISA 002 Study Team. Fluidity of HIV-1-Specific T-Cell Responses during Acute and Early Subtype C HIV-1 Infection and Associations with Early Disease Progression. J. Virol., 84(22):12018-12029, Nov 2010. PubMed ID: 20826686. Show all entries for this paper.

Displaying record number 57874

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef
Epitope	`KAAFDLSFF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF9
Subtype	C
Species (MHC/HLA)	human(B*58:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	CAP239: A01:01, A29:02, B42:01, B58:01, C06:02, C07:02; CAP217: A02:02, A29:01, B15:03, B58:01, C02:10, C06:02; CAP229: A01:23, A01:23, B58:01, B58:01, C06:02, C06:02
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, escape, acute/early infection

Notes

HLA-B*5801 is associated with slow progression. Six B*5801-positive subtype C-infected subjects were followed for up to 31 months from infection. CTL responses during acute infection predominantly targeted the TW10 and KF9 epitopes. Transmitted escape and compensatory mutations appeared to limit the protective effect of the B*5801 allele.
Longitudinal sequencing of KF9 from the 6 patients revealed variants that were assayed for EliSpot responses. Escape mutations (deletion -----LSFF, f|KAAFDLSFF, f|KAAFDLgFF, KgAvDLSFF, KAAvDLSFF, KvAFDLSFF, KgAFDLSFF, rAAFDLSFF) arose in KF9 in 4/6 subjects, and the two other subjects harbored escape mutations at the time of infection.
In EliSpot assays of overlapping peptides across the entire proteome, 5/6 patients targeted KF9, with 3/5 being confirmed single-peptide responses.

References

Chopera2011 D. R. Chopera, M. Mlotshwa, Z. Woodman, K. Mlisana, D. de Assis Rosa, D. P. Martin, S. Abdool Karim, C. M. Gray, C. Williamson, and CAPRISA 002 Study Team. Virological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals. J. Virol., 85(14):7070-7080, Jul 2011. PubMed ID: 21613398. Show all entries for this paper.

Displaying record number 58649

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location
Epitope	`KAAFDLSFF`	Epitope Alignment
Species (MHC/HLA)	human(B*58:01)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander noted this as an optimal B*5801 epitope based on data from Leslie2005a.

References

Displaying record number 56482

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef
Epitope	`KAAFDLSFF`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*58:01)
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).
KAAFDLSFF is a previously described HLA-B*5801-restricted epitope (part of Nef reacting peptide QVPLRPMTYKaAFDLSFFLKE) that contains a B*5801-associated reversion at residue A (KaAFDLSFF).

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 62133

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef(88-90)
Epitope	`KAAFDLSFF`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B*58:01)
Immunogen	HIV-1 infection
Experimental methods	Other, Relative replication capacity assay
Keywords	escape

Notes

Using the Ising and Potts models, the fitness landscape of HIV Nef protein (represented by 32 Nef mutations) was measured and validated against Nef-driven replication capacity, and Nef-mediated CD4 downregulation and HLA-I down-modulation. Model predictions correlated best with Nef-run relative replication and CD4 downregulation which was confirmed in a study of 448 patient-derived Nef sequences. Model prediction and fitness landscape correlation though present, is not as robust as in other HIV proteins.
Of the 448 patient-derived sequences, 298 were subtype C Nef sequences and 150 subtype B. For Subtype B, 5 additional Nef activities were measured: down-modulation of CXCR4 and CCR5, upregulation of CD74, enhancement of virion infectivity, and enhancement of viral replication, showing which Nef activities align with model predictions.
Position 88S was predicted to be a point of mutation, corroborated in Chopera2011 where epitope KAAFDLSFF, Nef 88-90, is a known escape, escaping to HLA A*01-KAAFDLgFF [Chopera et al. JV 85:7070-7078 (2011)]; [Carlson et al. Sc 345:6193 Suppl. Table 4 (2014)].
For mutation 88G, replication capacities, CD4 down-modulation capacities, and HLA-I down-modulation capacities expressed relative to that of the wild-type LANL consensus B Nef are 0.87, 0.997 and 0.941 respectively.

References

Barton2019 John P. Barton, Erasha Rajkoomar, Jaclyn K. Mann, Dariusz K. Murakowski, Mako Toyoda, Macdonald Mahiti, Phillip Mwimanzi, Takamasa Ueno, Arup K. Chakraborty, and Thumbi Ndung'u. Modelling and In Vitro Testing of the HIV-1 Nef Fitness Landscape. Virus Evol., 5(2):vez029, Jul 2019. PubMed ID: 31392033. Show all entries for this paper.

Displaying record number 61092

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef(82-90)
Epitope	`KAAFDLSFF`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	CH198: A03:01, A74:01, B08:01, B57, C07:01, C07:02
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	computational epitope prediction, escape, acute/early infection, mutation acquisition

Notes

17 patients with acute HIV-1 infection were followed to validate that (1) relative escape rate (2) location and identity of escape mutations and (3) epistatic effects on escape, could be predicted within a host by using a simple model based on population genetics and known fitness measures of HIV polyproteins. In general escape location was found most at residues with the lowest fitness cost and escape time correlates with early detection of mutants when T cell response was first detected.
Epitope KAAFDLSFF had a fitness cost ΔE of 3.005 and T cell response was first detected to it at 11d, escape time was 1 days.

References

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