Search CTL/CD8+ T-Cell Epitope Database

Found 31 matching records:

Displaying record number 60175

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(71-79)
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

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.
RPQVPLRPM had a significantly positive association with HLA B*07; it was recognized by 8/32 B*07-positive subjects and 15/228 B*07-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 56480

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPM`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B07, B8101)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	viral fitness and reversion, HLA associated polymorphism

Notes

HLA-associated polymorphisms were studied in a cohort of 710 chronic subtype C patients from South Africa. 84 HLA Class I-associated polymorphisms were identified, 73% of them with HLA-B. The viral set points associated with HLA allele correlated with the number of reversions associated with that allele, (HLA-B in Gag, HLA-C in Pol).
RPQVPLRPM is a previously described HLA-B*07 and -B*8101-restricted epitope (part of Nef reacting peptides EEEEGVGFPVrPQVPLRPMTY and VGFPVRPQVPlRPMTYKAAFD) that contain a B*07 and B*8101-associated reversion at residues R and L (rPQVPLRPM/RPQVPlRPM).

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 59044

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9-Nef
Subtype	B, C
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection
Country	Japan, South Africa, United Kingdom, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	binding affinity, subtype comparisons

Notes

HLA-B*0702 is associated with rapid progression to disease in B-clade HIV-1 infected subjects. B*0702+ C-clade infected subjects however are not associated with a high viral setpoint of infection, and target a broader range of Gag epitopes at higher magnitudes. Increased magnitudes of Nef-specific responses were also detected in C-clade infected B*0702+ cohorts. A C-clade specific, B*0702-restricted novel p17 epitope, RPGGKKHYM, RM9, was defined.
Epitope RM9, RPQVPLRPM, a B- and C-clade Nef epitope was targeted more by B-clade infected subjects than C-clade ones. The B-clade and C-clade consensus epitope is the same. Binding affinity of RM9 to B*0702 was K<sub>d</sub> = 13 nM. RM9 is contained within OLP76, EVGFPVRPQVPLRPMTYK in clade-B and EVGFPVRPQVPLRPMTfK in clade-C.

References

Kloverpris2014 Henrik N. Kløverpris, Emily Adland, Madoka Koyanagi, Anette Stryhn, Mikkel Harndahl, Philippa C. Matthews, Roger Shapiro, Bruce D. Walker, Thumbi Ndung'u, Christian Brander, Masafumi Takiguchi, Søren Buus, and Philip Goulder. HIV Subtype Influences HLA-B*07:02-Associated HIV Disease Outcome. AIDS Res. Hum. Retroviruses, 30(5):468-475, May 2014. PubMed ID: 24010680. Show all entries for this paper.

Displaying record number 57876

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPM`	Epitope Alignment
		Show epitope variants
Subtype	C
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, 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 from the 6 patients revealed variants that were assayed for EliSpot responses. An escape mutation (kPQVPLRP) in this epitope arose in 1/6 individuals.
In EliSpot assays of overlapping peptides across the entire proteome, 1/6 patients targeted a peptide containing this epitope.

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 53261

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef( C consensus)
Epitope	`RPQVPLRPM`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B0702, B4201, B*8101, B7, B81)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, HLA cross-presentation

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 either B07 or B81 tended to carry a variant of this epitope, while people who did not almost always carried the consensus form.
B*4201 may also present this epitope, as the allele is enriched in people who react with the peptide that contains the epitope, and it is known from the database to be also presented by B*4201.

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 62132

HXB2 Location	Nef(71-79)	Nef Epitope Map
Author Location	Nef(71-79)
Epitope	`RPQVPLRPM`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B0702, B8101)
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 76L was predicted to be a point of mutation, corroborated in Leslie2006 where epitope RPQVPLRPM, Nef 71-79, is a known escape, escaping to HLA-(B07 supertypes) B*4201/B*0702/B*8101-RPQVPvRPM, HLA B*4201/B*8101-RPQVPtRPM, HLA B*8101-RPQVPiRPM [Leslie et al. JI 177:4699-708. (2006)]; [Carlson et al. Sc 345:6193 Suppl. Table 4 (2014)].
For mutation 76V, 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 0.843, 1.006 and 0.931 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 doi, Jul 2019. PubMed ID: 31392033 Show all entries for this paper.

Displaying record number 56601

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(72-80)
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Subtype	C
Species (MHC/HLA)	human(B0702, B8101)
Immunogen	HIV-1 infection
Country	South Africa, Zambia
Experimental methods
Keywords	viral fitness and reversion, HLA associated polymorphism

Notes

A cohort of clade C-infected Zambian HIV-1 transmission pairs was studied. Accumulation in the donor of HLA-B restricted mutations in Gag, but not in Nef resulted in a reduced viral load in a recipient upon transmission.
20 mutations in Gag and 11 mutations in Nef, within or flanking CTL epitopes, were considered based on data from a Clade C South African cohort. HLA-B*0702-restricted RPQVPLRPM (RM9) was associated with a polymorphism at (R)PQVPLRPM, and HLA-B*8101-restricted RM9 was associated with a polymorphism at RPQVP(L)RPM.

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 59270

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Subtype	B
Species (MHC/HLA)	human(B*3501)
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 60172

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(71-79)
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Species (MHC/HLA)	human(B3502, B3503, B*5301)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

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.
RPQVPLRPM had a significantly positive association with HLA B*3502,B*3503,B*5301; it was recognized by 3/5 B*3502,B*3503,B*5301-positive subjects and 8/213 B*3502,B*3503,B*5301-negative subjects.

References

Displaying record number 60174

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(71-79)
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Species (MHC/HLA)	human(B*39)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

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.
RPQVPLRPM had a significantly positive association with HLA B*39; it was recognized by 4/19 B*39-positive subjects and 4/194 B*39-negative subjects.

References

Displaying record number 55160

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9 ?
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 54072

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	( C consensus)
Epitope	`RPQVPLRPM`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, optimal epitope

Notes

A comprehensive analysis of 160 class I T cell responses in 578 individuals from KwaZulu-Natal, South Africa was performed. Gag-specific responses were associated with lowering viremia, while Env, accessory and regulatory protein-specific responses were associated with higher viremia.
RPQVPLRPM is an optimal epitope for both B*4201 and B*4202.

References

Kiepiela2007 Photini Kiepiela, Kholiswa Ngumbela, Christina Thobakgale, Dhanwanthie Ramduth, Isobella Honeyborne, Eshia Moodley, Shabashini Reddy, Chantal de Pierres, Zenele Mncube, Nompumelelo Mkhwanazi, Karen Bishop, Mary van der Stok, Kriebashnie Nair, Nasreen Khan, Hayley Crawford, Rebecca Payne, Alasdair Leslie, Julia Prado, Andrew Prendergast, John Frater, Noel McCarthy, Christian Brander, Gerald H. Learn, David Nickle, Christine Rousseau, Hoosen Coovadia, James I. Mullins, David Heckerman, Bruce D. Walker, and Philip Goulder. CD8+ T-Cell Responses to Different HIV Proteins Have Discordant Associations with Viral Load. Nat. Med., 13(1):46-53, Jan 2007. PubMed ID: 17173051. Show all entries for this paper.

Displaying record number 54609

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Subtype	C
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Degranulation, CD107a and b cell surface mobilization, Intracellular cytokine staining, Proliferation, Tetramer binding
Keywords	rate of progression

Notes

Eight epitopes and 113 subjects were used to test whether correlations existed between HIV-1 Clade C viral load and CTL proliferation, cytokine production or degranulation in therapy-naive patients. Only CTL proliferation showed a strong inverse correlation with viral load.
The tetramer B*4201 RM9 was used to test 34 patients and gave a median ex vivo tetramer frequency of 0.22.

References

Day2007 Cheryl L. Day, Photini Kiepiela, Alasdair J. Leslie, Mary van der Stok, Kriebashne Nair, Nasreen Ismail, Isobella Honeyborne, Hayley Crawford, Hoosen M. Coovadia, Philip J. R. Goulder, Bruce D. Walker, and Paul Klenerman. Proliferative Capacity of Epitope-Specific CD8 T-cell Responses Is Inversely Related to Viral Load in Chronic Human Immunodeficiency Virus Type 1 Infection. J. Virol., 81(1):434-438, Jan 2007. PubMed ID: 17050606. Show all entries for this paper.

Displaying record number 55172

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	Intracellular cytokine staining, Proliferation, Tetramer binding
Keywords

Notes

PD-1 (inhibitory receptor programmed death) expression on CD8 and CD4 cells was studied. There was a positive correlation with viral load and inverse correlation with CD4 T cell count, and blockage of PD-1 pathway augmented CD4 and CD8 T cell function.

References

Day2006 Cheryl L. Day, Daniel E. Kaufmann, Photini Kiepiela, Julia A. Brown, Eshia S. Moodley, Sharon Reddy, Elizabeth W. Mackey, Joseph D. Miller, Alasdair J. Leslie, Chantal DePierres, Zenele Mncube, Jaikumar Duraiswamy, Baogong Zhu, Quentin Eichbaum, Marcus Altfeld, E. John Wherry, Hoosen M. Coovadia, Philip J. R. Goulder, Paul Klenerman, Rafi Ahmed, Gordon J. Freeman, and Bruce D. Walker. PD-1 Expression on HIV-Specific T Cells Is Associated with T-Cell Exhaustion and Disease Progression. Nature, 443(7109):350-354, 21 Sep 2006. PubMed ID: 16921384. Show all entries for this paper.

Displaying record number 56219

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location
Epitope	`RPQVPLRPM`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3001, A3303, B5301, B8101, Cw*0401
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.
RPQVPLRPM is a known HLA-B*4201-restricted epitope. Response to a peptide EVGFPVRPQVPLRPMTYKA containing this epitope is detected in an early controller (HLA alleles not determined) and an HLA-B*4201 negative 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 54608

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Subtype	C
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Degranulation, CD107a and b cell surface mobilization, Intracellular cytokine staining, Proliferation, Tetramer binding
Keywords	rate of progression

Notes

Eight epitopes and 113 subjects were used to test whether correlations existed between HIV-1 Clade C viral load and CTL proliferation, cytokine production or degranulation in therapy-naive patients. Only CTL proliferation showed a strong inverse correlation with viral load.
The tetramer B*4201 RM9 was used to test 34 patients and gave a median ex vivo tetramer frequency of 0.22.

References

Displaying record number 54104

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Species (MHC/HLA)	human(B*4201)
Immunogen
Experimental methods
Keywords	optimal epitope

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 59444

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(71-79)
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	Nef-RM9
Subtype	C
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Country	Botswana, South Africa, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Other, Tetramer binding
Keywords	immunodominance

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 RPQVPLRPM from OLP Nef-76 (EVGFPVRPQVPLRPM) had a targeting frequency of ˜43% of 154 HLA-B*4201⁺ subjects. Immunodominance rank was 4/20 tested epitopes.
Nef-RM9-HLA-B*4202's binding affinity, K_d = 3 nM; stability, K_1/2 = 22.4h.

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 58714

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(70-78)
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	Nef-RM9
Subtype	C
Species (MHC/HLA)	human(B4201, B4202)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3001, B4201, Cw1701; A3001, B4202, Cw1701
Country	Botswana, South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Tetramer binding
Keywords	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.
Nef epitope RM9, RPQVPLRPM, was recognized by > 50% of Nef/Vpr/Vif/Env/Pol HLA-B*4201- and by > 80% B*4202-positive responders, although the half life of RM9 binding B*4201 is longer than its half-life binding B*4202. This is the first report of RPQVPLRPM as restricted by HLA-B*4202.

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 58629

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location
Epitope	`RPQVPLRPM`	Epitope Alignment
Species (MHC/HLA)	(B*4202)
Immunogen
Experimental methods
Keywords	optimal epitope

Notes

C. Brander noted this as an optimal B*4202 epitope based on data from Kloverpris JV 2012.

References

Displaying record number 54073

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	( C consensus)
Epitope	`RPQVPLRPM`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*4202)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, optimal epitope

Notes

A comprehensive analysis of 160 class I T cell responses in 578 individuals from KwaZulu-Natal, South Africa was performed. Gag-specific responses were associated with lowering viremia, while Env, accessory and regulatory protein-specific responses were associated with higher viremia.
RPQVPLRPM is an optimal epitope for both B*4201 and B*4202.

References

Displaying record number 55975

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPM`	Epitope Alignment
		Show epitope variants
Epitope Name	TM9(Nef)
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	variant cross-reactivity

Notes

49 ART-naive chronically HIV-1 infected Chinese subjects' CTLs were tested with 413 OLPs in IFN-gamma 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.
Author defined epitope RPQVPLRPM elicited an immune response in Chinese HIV-1 positive subjects as part of peptide EVGFPVRPWVPLRPMTYK. This epitope differs from the previously described HLA-B7 epitope, TPQVPLRPM, at 1 residue, rPQVPLRPM.
7 of the 9 HLA-B7 carriers responded to rPQVPLRPM-containing peptide with average magnitude of CTL response of >370 SFC/million PBMC.

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 60178

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(71-79)
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Species (MHC/HLA)	human(B*78)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

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.
RPQVPLRPM had a significantly positive association with HLA B*78; it was recognized by 1/1 B*78-positive subjects and 1/186 B*78-negative subjects.

References

Displaying record number 60177

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(71-79)
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
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

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.
RPQVPLRPM had a significantly positive association with HLA B*81; it was recognized by 2/7 B*81-positive subjects and 2/187 B*81-negative subjects.

References

Displaying record number 57759

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPM`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*8101)
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.
Three B*8101-positive acutely HIV-1-infected individuals had a peptide response to presumed optimal epitope RPQVPLRPM within peptide EVGFPVRPQVPLRPMTYKA. Two had autologous viral escape, and one lost response at 13 weeks.

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 54624

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPM`	Epitope Alignment
		Show epitope variants
Epitope Name	RM9
Subtype	C
Species (MHC/HLA)	human(B*8101)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, escape, HLA associated polymorphism, elite controllers

Notes

To study whether CTL responses restricted by "good" HLA I molecules exert stronger immune selection than other HLA I molecules, 54 and 70 optimal epitopes within HIV-1 Gag, Pol and Nef genes for Caucasian and African cohorts were tested in patients over a mean of 14 months. "Good", advantageous HLA allele-restricted epitopes were much more polymorphic than epitopes restricted by other, non-advantageous HLA in patients, suggesting that benefits associated with HLA Class I alleles of elite controllers of disease progression are epitope-specific. Such "driver" epitopes with high polymorphism had high frequency of immune response, allowing them to be ranked for recognition and polymorphism.
Patients with higher proportions of mutated epitopes also had lower plasma viral loads, and mean epitope variability correlated negatively with relative hazard of disease progression.
Variant RPQVPvRPM at position 6 was the predominant polymorphism found.

References

Frater2007 A. J. Frater, H. Brown, A. Oxenius, H. F. Günthard, B. Hirschel, N. Robinson, A. J. Leslie, R. Payne, H. Crawford, A. Prendergast, C. Brander, P. Kiepiela, B. D. Walker, P. J. R. Goulder, A. McLean, and R. E. Phillips. Effective T-Cell Responses Select Human Immunodeficiency Virus Mutants and Slow Disease Progression. J. Virol., 81(12):6742-6751, Jun 2007. PubMed ID: 17409157. Show all entries for this paper.

Displaying record number 60176

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(71-79)
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Species (MHC/HLA)	human(B*82)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

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.
RPQVPLRPM had a significantly positive association with HLA B*82; it was recognized by 1/1 B*82-positive subjects and 0/185 B*82-negative subjects.

References

Displaying record number 60171

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(71-79)
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Species (MHC/HLA)	human(C*04)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

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.
RPQVPLRPM had a significantly positive association with HLA C*04; it was recognized by 23/81 C*04-positive subjects and 23/260 C*04-negative subjects.

References

Displaying record number 60173

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(71-79)
Epitope	`RPQVPLRPM`	Epitope Alignment
Epitope Name	RM9
Species (MHC/HLA)	human(C*17)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

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.
RPQVPLRPM had a significantly positive association with HLA C*17; it was recognized by 4/10 C*17-positive subjects and 11/218 C*17-negative subjects.

References

Displaying record number 57012

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef
Epitope	`RPQVPLRPM`	Epitope Alignment
Subtype	A1, CRF06_cpx, D
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Sweden
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, computational epitope prediction, vaccine antigen design

Notes

From HIV-1 sequences of multiple subtypes, bioinformatic prediction generated 174 CTL epitopes from Gag, Pol, Nef, Env and Tat restricted by HLA supertypes A1, A2, A3, A24, B7, B44 and B58; 10 previously-published A2- and B58-restricted epitopes were also included. Of these 184 epitopes, 113 were recognized experimentally in serum from 31 HIV+ patients.
While Gag, Pol, Env and Nef were highly immunogenic, only 38% of Tat epitopes elicited a response.
RPQVPLRPM was a predicted epitope restricted by B7 supertype. 3/31 patient(s) responded to it; all 3 responding patients were known to carry an allele of B7 supertype. Responding patients were infected with HIV clade(s) A1, D, CRF06_cpx.

References

Perez2008 Carina L. Pérez, Mette V. Larsen, Rasmus Gustafsson, Melissa M. Norström, Ann Atlas, Douglas F. Nixon, Morten Nielsen, Ole Lund, and Annika C. Karlsson. Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes. J. Immunol., 180(7):5092-5100, 1 Apr 2008. PubMed ID: 18354235. Show all entries for this paper.

Displaying record number 54193

HXB2 Location	Nef(71-79) DNA(9007..9033)	Nef Epitope Map
Author Location	Nef(71-79)
Epitope	`RPQVPLRPM`	Epitope Alignment
		Show epitope variants
Epitope Name	RM9
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, escape, 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.
Functional avidity is correlated with selection pressure observed in HLA allele-epitope restriction.
For this epitope, RM9, selection pressure was evidenced by studying changing epitope variants associated with HLAs of the B7 supertype.
Higher level of sequence variation and escape mutations were associated with the B*8101 and B*0702 alleles.
Statistically significant associations between numbers of HLA-B8101, -0702 and -B4201 expressing subjects and epitope RPQVPLRPM were found.
In 3 B-supertype alleles studied, B*4201, B*8101 and B*0702, two RM9 variants were most common - one at the first position, kPQVPLRPM and the other at the sixth position, RPQVPvRPM. Several more variants are listed in the paper.

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.