Search CTL/CD8+ T-Cell Epitope Database

Found 4 matching records:

Displaying record number 54579

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HXB2 Location	Gag(93-101) p17(93-101) DNA(1066..1092)	Gag Epitope Map
Author Location	Gag(93-101)
Epitope	EVKDTKEAL	Epitope Alignment
		Show epitope variants
Epitope Name	EL9
Subtype	B
Species (MHC/HLA)	human(B*08)
Immunogen	HIV-1 infection
Patient MHC/HLA	A*01, A*02
Country	United States
Experimental methods	Intracellular cytokine staining, Other
Keywords	rate of progression, escape, mutation acquisition

Notes

• To correlate evolving HIV-1 populations with HLA-A2 restricted immune responses for epitopes in Gag, Pol, Env and Nef, 11 treatment-naive subjects were longitudinally studied. Results show that increased viral load is often associated with broad CTL responses early in infection that persist as an "immunological footprint". Conversely, early, restricted responses may help limit viral load. Phylogenetic and functional evidence of viral escape is seen in Gag, Nef and Pol. Gag and Nef show flanking epitope changes restricted by non-HLA-A2 alleles. As far as modes of viral adaptation, CTL responses were seen to develop both against static viral populations resulting in viral evolution to HLA-A2 as well as against existing mutants resulting in reselection of consensus B-like variants. This study reinforces that CTL immune responses detected are not necessarily beneficial to patients, but may be "footprints" from early effective responses that the virus has since escaped.
• A minor response was detected against an E93D variant of this epitope, dVKDTKEAL. However, CTL responses effectively eliminated cells with this viral variant. Upstream of this epitope, EVKDTKEAL, an R91G mutation was seen that is suggested to affect processing of this EL9 epitope, such that this mutant viral population evaded immune responses restricted by HLAs A*01, A*02 and B*08. Other variants detected were EiKDTKEAL, kVKDTKEAL and EVKDTKgAL.

References

Karlsson2007 Annika C. Karlsson, Astrid K. N. Iversen, Joan M. Chapman, Tulio de Oliviera, Gerald Spotts, Andrew J. McMichael, Miles P. Davenport, Frederick M. Hecht, and Douglas F. Nixon. Sequential Broadening of CTL Responses in Early HIV-1 Infection Is Associated with Viral Escape. PLoS ONE, 2:e225, 2007. PubMed ID: 17311088. Show all entries for this paper.

Displaying record number 53230

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HXB2 Location	Gag(93-101) p17(93-101) DNA(1066..1092)	Gag Epitope Map
Author Location	Gag(99-107 WEAU)
Epitope	EVKDTKEAL	Epitope Alignment
Epitope Name	Gag EVL9
Subtype	B
Species (MHC/HLA)	human(B*08:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	WEAU: A01, A29, B08, B44
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	dynamics, acute/early infection, kinetics, autologous responses, optimal epitope

Notes

• Primary CD8+ T-cell response to Env, Tat and Gag and the extent, kinetics and mechanisms of viral escape were examined in three patients. Rapid escape, within weeks from infection, from HIV specific CTL responses was observed in all three patients, but the kinetics and extent of the escape differed depending on the breadth and co-dominant distribution of CTL-mediated pressure. The two patients that rapidly declined had more focused immunodominant responses, while the single patient that had low viral load and stable CD4 counts for seven years had a broad co-dominant response and less escape.
• The patient WEAU had high viral loads and rapid CD4 decline. WEAU mounted 14 detected CTL responses, with distinct patterns of immunodominance. WEAU did not control viral replication well, and escape mutations occurred early and 4/14 had changes that could have resulted in escape, and two were confirmed as escape.
• There was a weak response to this epitope during acute and early infection, and the epitope sequence did not vary during the first year of the infection.
• Dynamics of this response are shown in Fig. S2 of Yang2019 which developed mathematical models with data from Jones2004. Yang2019 concluded that, in general, relative CTL response breadth increased moderately during the first symptomatic month and then remained relatively stable through the first 400 days post-infection. Analysis also suggested slow expansion kinetics for most HIV-specific CTL responses and the presence of intra- and interclonal competition.

References

Jones2004 Nicola A. Jones, Xiping Wei, Darren R. Flower, MaiLee Wong, Franziska Michor, Michael S. Saag, Beatrice H. Hahn, Martin A. Nowak, George M. Shaw, and Persephone Borrow. Determinants of Human Immunodeficiency Virus Type 1 Escape from the Primary CD8+ Cytotoxic T Lymphocyte Response. J. Exp. Med., 200(10):1243-1256, 15 Nov 2004. PubMed ID: 15545352. Show all entries for this paper.

Yang2019 Yiding Yang, and Vitaly V. Ganusov. Defining Kinetic Properties of HIV-Specific CD8(+) T-Cell Responses in Acute Infection. Microorganisms, 7(3):microorganisms7030069 doi, Mar 2019. PubMed ID: 30836625 Show all entries for this paper.

Displaying record number 53822

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HXB2 Location	Gag(93-101) p17(93-101) DNA(1066..1092)	Gag Epitope Map
Author Location	p17
Epitope	EVKDTKEAL	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(B*08:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A*01:01, A*03:01, B*08:01, B*51:01; A*01:01, B*08:01
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	escape, acute/early infection, variant cross-reactivity

Notes

• CTL responses and escape were analyzed in 4 homosexual couples where blood samples were available within weeks of estimated transmission. When the recipient had the same HLA type as the donor, CTL escape variants prevented a CTL response to those epitopes in the recipient. Even when the HLA alleles were different in the transmitting couple, a single escape mutation in one epitope can abolish CTL recognition of an overlapping epitope of distinct restriction in the recipient. In an early acute infection of the donor, the precise timing of transmission determines the viral variants transmitted.
• The second donor in the study shares A*0101 and B*0801 with his partner. The epitope EVKDTKEAL has an escape variant in the donor that does not react in an Elispot assay, DvkGtkeal, but the Dvkdtkeal form was the transmitted variant. The transmitted form and EVKDTKEAL bind with equal affinity to B*0801.
• The recipient mounted a response to the Dvkdtkeal form of the epitope. The variant DvRdtkeal was detected by 32 weeks post infection.

References

Milicic2005 Anita Milicic, Charles T. T. Edwards, Stéphane Hué, Julie Fox, Helen Brown, Tilly Pillay, Jan W. Drijfhout, Jonathan N. Weber, Edward C. Holmes, Sarah J. Fidler, Hua-Tang Zhang, and Rodney E. Phillips. Sexual Transmission of Single Human Immunodeficiency Virus Type 1 Virions Encoding Highly Polymorphic Multisite Cytotoxic T-Lymphocyte Escape Variants. J. Virol., 79(22):13953-13962, Nov 2005. PubMed ID: 16254331. Show all entries for this paper.

Displaying record number 58197

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HXB2 Location	Gag(93-101) p17(93-101) DNA(1066..1092)	Gag Epitope Map
Author Location	Gag/Pol(94- CDC-451)
Epitope	EVKDTKEAL	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	computer prediction
Experimental methods
Keywords	T-cell crossreactivity to human proteins

Notes

• The paper defines potential crossreactivity between HIV-1 and human host proteins. HIV B-clade strain CDC-451 shares 50 7mers and 3 8mers with the human proteome. Of these, 35 are within experimentally-validated epitopes targeted by human immune responses to HIV. The number of common 7mers between the proteomes is 3.7-fold higher than would be expected by chance.
• The 7mers in common with HIV are present in human proteins that, when altered, are associated with AIDS-related symptoms, suggesting that disease symptoms may be caused by autoimmune responses.
• Previously-documented CTL epitope EVKDTKEAL contains 7mer RDTKEAL, which occurs in human gene STRN: Striatin (acts in dendritic Ca2+ signaling). This protein is involved in Ca2+ signaling in the brain and may be involved in the frequency of comorbidity of HIV infection and schizophrenia.

References

Lucchese2011 Guglielmo Lucchese, Angela Stufano, Michele Calabro, and Darja Kanduc. Charting the Peptide Crossreactome between HIV-1 and the Human Proteome. Front. Biosci. (Elite Ed.), 3E:1385-1400, 2011. PubMed ID: 21622144. Show all entries for this paper.