Search CTL/CD8+ T-Cell Epitope Database

Found 18 matching records:

Displaying record number 57736

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPMTY`	Epitope Alignment
		Show epitope variants
Epitope Name	RY11
Species (MHC/HLA)	human(B*35)
Immunogen
Experimental methods
Keywords	review

Notes

This mini-review focuses on the changing interplay between viral adaptation and host selective CTL pressure. It also discusses biochemical and biophysical properties of peptide-MHC I interaction.
Since CTL responses correlate with VL (viral load) control in acute but not chronic HIV-1 infections, the functional defect that occurs in CTL over time is studied and noted that successive waves of CTL specificity to different epitopes could be the outcome of initial epitopes' mutating to escape. Besides CTL antiviral activity, their cross-reactive properties are also implicated in VL control.
Antiviral CTL activity as correlated with peptide-MHC I interactions seem to be influenced by the peptide-off rate, where a delayed decay makes target cells more susceptible to CTL-mediated killing. The importance of thermostability data during peptide unfolding is discussed.
Epitope RY11, RPQVPLRPMTY, with moderate antiviral activity becomes immunodominant in chronic infection after the loss of activity of overlapping VY8, VPLRPMTY, that CTL are cross-reactive to.

References

Motozono2010 Chihiro Motozono, Philip Mwimanzi, and Takamasa Ueno. Dynamic Interplay between Viral Adaptation and Immune Recognition during HIV-1 Infection. Protein Cell, 1(6):514-519, Jun 2010. PubMed ID: 21204005. Show all entries for this paper.

Displaying record number 58619

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPMTY`	Epitope Alignment
Epitope Name	RY11
Subtype	B
Species (MHC/HLA)	human(B*35)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander noted this as an optimal B*3501 epitope based on data from Motozono2009.

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 55694

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef(75-85)
Epitope	`RPQVPLRPMTY`	Epitope Alignment
		Show epitope variants
Epitope Name	RY11
Species (MHC/HLA)	human(B*35)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	CTL suppression of replication, Cytokine production, HLA binding, Intracellular cytokine staining, Other, Tetramer binding
Keywords	class I down-regulation by Nef, escape

Notes

The balance between Nef selective pressures to modulate HLA I or its escape mutations reducing Nef HLA I down-regulating activity is studied.
Epitope RY11 does not share CTL with VY8 (VPLRPMTY), but is a different optimal epitope. RY11 shows less functional avidity than VY8. No subject showed an immune response to both epitopes simultaneously.
Epitope RPQVPLRPMTY escape mutations at T75 (tPQVPLRPMTY) and F85 (RPQVPLRPMTf), are associated with HLA-B*35. Mutations tend to go from RF to TY and double mutants are rare. Only the double mutant, TF (tPQVPLRPMTf), however, diminishes Nef-mediated surface HLA-I down-regulation.
VY-8F (VPLRPMTf) and RY-11F (RPQVPLRPMTf) do not change HLA-binding activity, but RY11-1T (tPQVPLRPMTY) does increase binding by ~10.

References

Ueno2008 Takamasa Ueno, Chihiro Motozono, Sachi Dohki, Philip Mwimanzi, Susanne Rauch, Oliver T. Fackler, Shinichi Oka, and Masafumi Takiguchi. CTL-Mediated Selective Pressure Influences Dynamic Evolution and Pathogenic Functions of HIV-1 Nef. J. Immunol., 180(2):1107-1116, 15 Jan 2008. PubMed ID: 18178851. Show all entries for this paper.

Displaying record number 967

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef(75-85 SF2)
Epitope	`RPQVPLRPMTY`	Epitope Alignment
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Binds HLA-B*3501.

References

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 971

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	( SF2)
Epitope	`RPQVPLRPMTY`	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.
rpqvplrpmtF was found in 9/10 of the B35+ individuals, none of the B35- individuals---the Y-->F substituted peptide had a similar binding affinity with B35 and was recognized by a CTL clone equally with wildtype.

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 1420

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef(69-79)
Epitope	`RPQVPLRPMTY`	Epitope Alignment
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

One of the 51 HIV-1 epitopes selected by Ferrari et al. as good candidate CTL epitopes for vaccines by virtue of being conserved and presented by common HLA alleles.

References

Ferrari2000 G. Ferrari, D. D. Kostyu, J. Cox, D. V. Dawson, J. Flores, K. J. Weinhold, and S. Osmanov. Identification of highly conserved and broadly cross-reactive HIV type 1 cytotoxic T lymphocyte epitopes as candidate immunogens for inclusion in Mycobacterium bovis BCG-vectored HIV vaccines. AIDS Res. Hum. Retroviruses, 16(14):1433-43, 20 Sep 2000. PubMed ID: 11018863. Show all entries for this paper.

Displaying record number 57333

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef(75-)
Epitope	`RPQVPLRPMTY`	Epitope Alignment
		Show epitope variants
Epitope Name	Nef75
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	Chromium-release assay, Cytotoxicity assay, Intracellular cytokine staining, Proliferation, Tetramer binding
Keywords	binding affinity, escape

Notes

CTL responses toward B35 optimal epitopes in Pol, Env, and Nef were characterized in chronically-infected patients. Antigenic variations that abolished TCR recognition not only resulted in escape but also eventually generated a subset of variant-specific CTLs having decreased antiviral activity.
In a tetramer analysis of RPQVPLRPMTY, the average response frequency of B35-positive HIV-1-infected patients was significantly above background. This epitope had the highest response frequency among the 5 B35 epitopes studied.
Escape variant tPQVPLRPMTY was documented on the basis of sequence frequency in B35-positive patients, abolished TCR binding, flow cytomeric assay, and cytotoxicity assay.

References

Ueno2007 Takamasa Ueno, Yuka Idegami, Chihiro Motozono, Shinichi Oka, and Masafumi Takiguchi. Altering Effects of Antigenic Variations in HIV-1 on Antiviral Effectiveness of HIV-Specific CTLs. J. Immunol., 178(9):5513-5523, 1 May 2007. PubMed ID: 17442933. Show all entries for this paper.

Displaying record number 57338

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPMTY`	Epitope Alignment
Epitope Name	RY11
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	Cytokine production, Cytotoxicity assay, Other, Tetramer binding
Keywords	binding affinity, TCR usage, optimal epitope

Notes

VY8 (VPLRPMTY) and RY11 (RPQVPLRPMTY) are overlapping B35 epitopes. Analysis of CTL clones recognizing the two epitopes showed that they are both optimal epitopes recognized by different sets of CTL clones.
In 4 chronically-infected B*3501-positive patients, VY8-specific CTL clones had higher cytotoxicity than RY11-specific CTL clones.

References

Motozono2009 Chihiro Motozono, Saeko Yanaka, Kouhei Tsumoto, Masafumi Takiguchi, and Takamasa Ueno. Impact of Intrinsic Cooperative Thermodynamics of Peptide-MHC Complexes on Antiviral Activity of HIV-Specific CTL. J. Immunol., 182(9):5528-5536, 1 May 2009. PubMed ID: 19380801. Show all entries for this paper.

Displaying record number 58169

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef(75-85 JRFL-SF2nef)
Epitope	`RPQVPLRPMTY`	Epitope Alignment
		Show epitope variants
Epitope Name	RY11
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infected monocyte-derived
Experimental methods	Cytotoxicity assay, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	class I down-regulation by Nef, immunodominance

Notes

In HIV patients with B35, Nef elicits dominant responses toward early epitope VPLRPMTY (VY8), followed by the longer, overlapping epitope RPQVPLRPMTY (RY11). The study examined Nef-mediated CTL activity toward monocyte-derived macrophages infected with HIV-1 strain JRFL-SF2nef.
RY11-specific CTLs showed toxicity toward HIV-infected macrophages, but failed to kill tPQVPLRPMTY or tPQYPLRPMTf mutant virus-infected cells.
Cell surface expression of CCR5 was reduced in virus-infected macrophages with wild type Nef. The Y81F mutant had similar down-regulation, but the R71T and Y81F/R71T double mutants lacked the downregulatory activity. CD4 downregulatory activity was not affected by any of the mutants.

References

Mwimanzi2011 Philip Mwimanzi, Zafrul Hasan, Ranya Hassan, Shinya Suzu, Masafumi Takiguchi, and Takamasa Ueno. Effects of Naturally-Arising HIV Nef Mutations on Cytotoxic T Lymphocyte Recognition and Nef's Functionality in Primary Macrophages. Retrovirology, 8:50, 2011. PubMed ID: 21696586. Show all entries for this paper.

Displaying record number 62131

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef(71-81)
Epitope	`RPQVPLRPMTY`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B35)
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 71R was predicted to be a point of mutation, corroborated in Ueno2007 and Mwimanzi2001 where epitope RPQVPLRPMTY, Nef 71-81, is a known escape, escaping to HLA Cw*0702-kPQVPLRPMTY [Ueno et al. JI 178:5513-23. (2007)] or B*0702-tPQVPLRPMTY [Mwimanzi et al. Retrovirology 8:50. (2011)]. The R71K mutant is also associated with B*44 and Cw*17 [Carlson et al. Sc 345:6193 Suppl. Table 4 (2014).].
For mutation 71K, 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 0.854, 1.002 and 0.972 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 1342

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef(75-85)
Epitope	`RPQVPLRPMTY`	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 57805

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPMTY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	computational epitope prediction, HLA associated polymorphism

Notes

From a large study of HLA-associated polymorphisms, 431 putative epitopes with good EpiPred scores were selected; 320 of these were tested for IFNgamma EliSpot responses in subjects carrying the predicted HLA.
Peptides with response rate >40% (comparable with mean response rate of 33% for known epitopes) and tested in 5 or more individuals with respective HLA were considered in this study as probable novel epitopes and entered in the database. 41 additional "possible" novel epitopes for which either <5 individuals were tested or response rate was below 40%, are not entered in the database.
There was a markedly higher proportion of putative epitopes in Nef, and the Nef epitopes tended to have the most high-magnitude EliSpot responses. Among 33 epitopes that elicited a response in over 40% out of 5 or more individuals tested, over 61% clustered in Nef.
Epitope RPQVPLRPMTY was recognized by 10/13 B*3501-positive HIV-1-infected patients.

References

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

Displaying record number 61889

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef(71-81)
Epitope	`RPQVPLRPMTY`	Epitope Alignment
		Show epitope variants
Epitope Name	RY11
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.
Nef epitope RPQVPLRPMTY (RY11) elicited CTL response in 32/63 HLA-B*3501+ HIV-1-infected ART naive Japanese subjects, and a significant association was found with suppression of pVL (plasma viral load).
NefY81F in variant RPQVPLRPMTf has little impact on suppression of HIV-1 by RY11-specific CTL.
The HLA-A*2402-associated polymorphism NefY135F which is seen in epitope YF9, fPLTFGWCF accumulates in B*3501+ Japanese individuals to 61% and is strongly associated with lower pVL and RY11-specific CTL responses. Thus RY11-specific CTL can suppress the replication of the Y135F mutant virus.

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 968

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef(75-85 SF2)
Epitope	`RPQVPLRPMTY`	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.
4/7 B35-positive individuals had a strong CTL response to this epitope.
An R to T substitution at position 1 abrogates specific lysis, but not binding to B*3501.
An R to H substitution at position 7 did not alter reactivity.

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 59269

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPMTY`	Epitope Alignment
Epitope Name	RY11
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	Flow cytometric T-cell cytokine assay, HLA binding, TCR binding, Tetramer binding
Keywords	structure

Notes

Length of epitope was shown to be related to TCR's peptide recognition footprints. While TCR cross reactivity was similar within the same peptide length type, it was markedly different between different peptide length types.
RY11 is located in an immunodominant region of Nef, and contains two other B35-restricted epitopes, RM9 and VY8. An HLA stabilization assay revealed that RY11 and RM9 bound to HLA with similar affinity, but VY8 was lower. Five CTL clones from 4 B*3501-positive patients all showed activity against RY11; 2 clones showed more potent activity against VY8.

References

Motozono2014 Chihiro Motozono, Masaru Yokoyama, Hironori Sato, and Takamasa Ueno. Cross-Reactivity Analysis of T Cell Receptors Specific for Overlapping HIV-1 Nef Epitopes of Different Lengths. Microbes Infect., 16(4):320-327, Apr 2014. PubMed ID: 24380790. Show all entries for this paper.

Displaying record number 57672

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	( SF2)
Epitope	`RPQVPLRPMTY`	Epitope Alignment
		Show epitope variants
Epitope Name	RY11
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	Chromium-release assay, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	class I down-regulation by Nef, superinfection, HLA associated polymorphism

Notes

The influence of naturally-arising Nef mutations on the viral receptor down-regulation activity and the protection from superinfection was studied.
R75T and Y85F in SF2 numbering (R71T and Y81F in HXB2 numbering) were significantly over-represented in HLA-B*3501-positive subjects (out of 235 subjects in Japan).
RPQVPLRPMTY-specific CTLs did not respond to cells expressing tPQVPLRPMTY and tPQVPLRPMTf variants. For the shorter epitope VY8 VPLRPMTY, VPLRPMTY-specific CTL clones did not recognize the cells expressing RPQVPLRPMTf and tPQVPLRPMTf variants, indicating that R71T and Y81F confer escape from HLA B*3501-restricetd CTLs.
R71T variant Nef selectively impaired CCR5 but not CXCR4 down-regulation activity, whereas Y81F variant Nef affected neither CCR5 nor CXCR4 down-regulation activity. Moreover, the cells expressing the Y81F variant Nef significantly impaired protection from superinfection by CCR5-tropic, but not CXCR4-tropic, viruses.

References

Mwimanzi2010 Philip Mwimanzi, Zafrul Hasan, Michiyo Tokunaga, Hiroyuki Gatanaga, Shinichi Oka, and Takamasa Ueno. Naturally Arising HIV-1 Nef Variants Conferring Escape from Cytotoxic T Lymphocytes Influence Viral Entry Co-Receptor Expression and Susceptibility to Superinfection. Biochem. Biophys. Res. Commun., 403(3-4):422-427, 17 Dec 2010. PubMed ID: 21093412. Show all entries for this paper.

Displaying record number 52433

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPMTY`	Epitope Alignment
Subtype	A, B, D
Species (MHC/HLA)	human, macaque(B51)
Immunogen	HIV-1 infection, vaccine
Experimental methods
Keywords	subtype comparisons, epitope processing, vaccine-induced immune responses, immunodominance

Vaccine Details

Vaccine type	DNA prime with modified vaccinia Ankara (MVA) boost
Vaccine strain	A clade
Vaccine component	p17 Gag, p24 Gag

Notes

The HIV-1 subtype A focused vaccine HIVA contains p24 and p17, in a reversed order relative to the Gag polyprotein to prevent myristylation of p17, which could direct the protein to the cell membrane and inhibit efficient peptide processing and class I presentation, as well as a polyepitope string of conserved, often immunodominant epitopes that were selected to have particularly good cross-reactive potential for the A-clade epidemic in Nairobi, Kenya. A DNA and MVA prime-boost vaccination protocol using the HIVA antigen will be used in a phase III clinical trial in Kenya. This epitope is included in the polyepitope string Hanke2000.
Multiple CD4+ or CD8+ T-cell vaccine-induced responses to peptide pools were detected using intracellular cytokine staining and IFNgamma Elispot assays after vaccination of 5 macaques. The response to the Mamu A*01 SIV p27 epitope p11C (CTPYDINQM), included in the polyepitope region, was not immunodominant in the Mamu A*01 vaccinated macaques, possibly because of processing limitations in context of the artificial polyepitope string Wee2002.

References

Hanke2000 Tomas Hanke and Andrew J. McMichael. Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya. Nat. Med., 6(9):951-955, Sep 2000. PubMed ID: 10973301. Show all entries for this paper.

Wee2002 Edmund G.-T. Wee, Sandip Patel, Andrew J. McMichael, and Tomáš Hanke. A DNA/MVA-Based Candidate Human Immunodeficiency Virus Vaccine for Kenya Induces Multi-Specific T Cell Responses in Rhesus Macaques. J. Gen. Virol., 83(Pt 1):75-80, Jan 2002. PubMed ID: 11752703. Show all entries for this paper.

Displaying record number 59228

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HXB2 Location	Nef(71-81) DNA(9007..9039)	Nef Epitope Map
Author Location
Epitope	`RPQVPLRPMTY`	Epitope Alignment
		Show epitope variants
Epitope Name	RY11
Subtype	B
Species (MHC/HLA)	human
Immunogen	peptide-HLA interaction
Experimental methods	HLA binding, Other
Keywords	structure

Notes

A dehydrated minor state of the HLA-B*3501-RY11 complex newly identified by three-dimensional transverse relaxation-optimized dispersion NMR spectroscopy (TROSY) undergoes site-specific conformational fluctuations that are responsible for peptide-dependent stabilization of HLA-B*3501. B*3501-RY11(RPQVPLRPMTY) shares a similar buried surface area (BSA) to B*3501/VY8 and 20 other B*3501-peptide complexes but is less thermostable. The larger the minor population of HLA-peptide complex, the longer pHLA complexes were present on the cell surface.

References

Yanaka2014 Saeko Yanaka, Takamasa Ueno, Yi Shi, Jianxun Qi, George F. Gao, Kouhei Tsumoto, and Kenji Sugase. Peptide-Dependent Conformational Fluctuation Determines the Stability of the Human Leukocyte Antigen Class I Complex. J. Biol. Chem., 289(35):24680-24690, 29 Aug 2014. PubMed ID: 25028510. Show all entries for this paper.