Search CTL/CD8+ T-Cell Epitope Database

Found 4 matching records:

Displaying record number 59183

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HXB2 Location	Nef(188-196) DNA(9358..9384)	Nef Epitope Map
Author Location	Nef(188-196 NL432)
Epitope	SLAFRHVAR	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*31)
Immunogen	HIV-1 infection
Patient MHC/HLA	AC05: A*24:02, A*31:01, B*39:01, B*52:01, C*07:02, C*12:02; AC08: A*02:01, A*31:01, B*08:01, B*44:02, C*05, C*07
Country	Australia, Germany, United States
Experimental methods	Other
Keywords	class I down-regulation by Nef, acute/early infection

Notes

• 10 acute controllers (AC) were compared to 50 acute progressors to analyze Nef function and downregulation of HLA Class I and CD4 levels. Nef-specific CTL of acute controllers downregulated HLA-I and CD4 less; with reduced virion infectivity. HLA-associated polymorphisms in Nef did effect impaired immune function in some controllers. In general however, controllers (6/10) had less Nef-induced viremic effects, due probably to host CTL pressure response.
• Published A*31-restricted epitope SLAFRHVAR (Nef 188-196) contains a V194A variation, (while variation M182L resides in a predicted A*31-restricted Nef 178-189 epitope, KEVLMKFDTRL), the autologous sequence withing AC01 is tLAFhHVAR.

References

Kuang2014 Xiaomei T. Kuang, Xiaoguang Li, Gursev Anmole, Philip Mwimanzi, Aniqa Shahid, Anh Q. Le, Louise Chong, Hua Qian, Toshiyuki Miura, Tristan Markle, Bemuluyigza Baraki, Elizabeth Connick, Eric S. Daar, Heiko Jessen, Anthony D. Kelleher, Susan Little, Martin Markowitz, Florencia Pereyra, Eric S. Rosenberg, Bruce D. Walker, Takamasa Ueno, Zabrina L. Brumme, and Mark A. Brockman. Impaired Nef Function Is Associated with Early Control of HIV-1 Viremia. J. Virol., 88(17):10200-10213, 1 Sep 2014. PubMed ID: 24965469. Show all entries for this paper.

Displaying record number 56635

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HXB2 Location	Nef(188-196) DNA(9358..9384)	Nef Epitope Map
Author Location	Nef(187-196)
Epitope	SLAFRHVAR	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(A*31:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A*02:01, A*31:01, B*40:01, B*44:02, C*03:02, C*05:01
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	escape, acute/early infection, novel epitope

Notes

• Using overlapping 15-mer peptides, CTL responses to early, acute HIV infection were determined. Early virus escape attributed to CTL response was charted and subsequent clusters of mutations due to NAb targeting were also found.
• Five findings made: (i) exact numbers of transmitted HIV-1 actual and potential T cell epitopes were determined (ii) CTL-mediated virus escape occurring as viremia peaks, drops and reaches set point earlier and faster than previously known (iii) CTL responses to some transmitted virus epitopes were lost after early escapes were selected (iv) a few unexplained escapes were probably due to bystander mutations (v) earliest CTL responses cause the decline of VL in acute infection.
• This transmitted, newly predicted epitope, SLAFRHVAR, was studied in patient CH40 as part of peptide Nef(185-202) FDSSLAFRHVARELHPEY. Within 14 days the majority of sequences contained an R192H substitution to the clade B consensus. Founder, SLAFRHVAR, was completely lost by 29d; instead R196Q and S188R/N forms predominated.
• Escape mutations of SLAFRHVAR seen in Patient CH40 were SSLAFhHVAR, SLAFRHVAq, SrLAFRHVAR and SnLAFRHVAR, and all were not recognized by CTL.

References

Goonetilleke2009 Nilu Goonetilleke, Michael K. P. Liu, Jesus F. Salazar-Gonzalez, Guido Ferrari, Elena Giorgi, Vitaly V. Ganusov, Brandon F. Keele, Gerald H. Learn, Emma L. Turnbull, Maria G Salazar, Kent J Weinhold, Stephen Moore, CHAVI Clinical Core B, Norman Letvin, Barton F. Haynes, Myron S. Cohen, Peter Hraber, Tanmoy Bhattacharya, Persephone Borrow, Alan S. Perelson, Beatrice H. Hahn, George M. Shaw, Bette T. Korber, and Andrew J. McMichael. The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J. Exp. Med., 206(6):1253-1272, 8 Jun 2009. PubMed ID: 19487423. Show all entries for this paper.

Displaying record number 62130

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HXB2 Location	Nef(188-196) DNA(9358..9384)	Nef Epitope Map
Author Location	Nef(188-196)
Epitope	SLAFRHVAR	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(A*31:01)
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 188S was predicted to be a point of mutation, corroborated in Goonetilleke2009 [Goonetilleke et al. JEM 206:1253-72 (2009)] where epitope SLAFRHVAR , Nef 188-196, is a known escape, escaping as S188R/N to S|rLAFRHVAR or S|nLAFRHVAR, associated with HLAs B*5801 and A*3101 respectively. The most common mutation seen is hLAFRHVAR which Carlson2014 and Carlson2012a report as being associated with B*1510 and B*1801 [Carlson et al. Sc 345:6193 Suppl. Table 4 (2014).], and A*3101 [Carlson et al. JVI 86(24):13202 Suppl Table 3 (2012)].

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 57431

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HXB2 Location	Nef(188-196) DNA(9358..9384)	Nef Epitope Map
Author Location	Nef
Epitope	SLAFRHVAR	Epitope Alignment
		Show epitope variants
Epitope Name	SR9
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	United States
Experimental methods
Keywords	escape, acute/early infection

Notes

• 3 subjects with acute HIV infection were studied longitudinally by 454-ultra deep-sequencing of 4 HIV-1 epitope regions that have early recognition and escape. Over 50 variant forms of each CTL epitope targeted during the first 3-6 weeks of infection were found, i.e. 7-25 times more than variation in the control V3 region of Env, at earlier times. In very early infection, reversions were seen where immune pressure was considerable but they were absent outside epitopes. A strong case was made for establishment of infection via a single virus.
• All 3 subjects' epitopes have been tested as published previously.
• Epitope SLAFRHVAR from patient CH40 is thought to be the transmitted, susceptible epitope form and is recognized in EliSpot assay. It has an estimated accumulation or loss rate of -0.3. 4 escape lineages from this epitope are SSLAFRHVA[R/Q] and SSLAF[R/H]HVAR. Immune selection is estimated to have begun by day 5 postinfection, and escapes accrued swiftly.

References

Fischer2010 Will Fischer, Vitaly V. Ganusov, Elena E. Giorgi, Peter T. Hraber, Brandon F. Keele, Thomas Leitner, Cliff S. Han, Cheryl D. Gleasner, Lance Green, Chien-Chi Lo, Ambarish Nag, Timothy C. Wallstrom, Shuyi Wang, Andrew J. McMichael, Barton F. Haynes, Beatrice H. Hahn, Alan S. Perelson, Persephone Borrow, George M. Shaw, Tanmoy Bhattacharya, and Bette T. Korber. Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-Deep Sequencing. PLoS One, 5(8):e12303, 2010. PubMed ID: 20808830. Show all entries for this paper.