Search T Helper/CD4+ T-Cell Epitope Database

Found 3 matching records:

Displaying record number 481

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HXB2 Location	gp160(322-336) gp120(322-336) DNA(7188..7232)	gp160 Epitope Map
Author Location	Env( 1007)
Epitope	IIGDIRQAHCNISRE	Epitope Alignment
Species (MHC/HLA)	mouse(H-2 IAb)
Immunogen	vaccine
Experimental methods
Keywords	subtype comparisons, epitope processing, TCR usage

Vaccine Details

Notes

• This epitope is located in the V3 region of 1007 (US, clade B) and was recognized by three hybridomas with Vβ usage Vβ 6 and not determined.
• C57BL/6 mice were immunized with a prime-boost strategy involving three HIV-1 Env antigens: Mice were primed with DNA given i.m., 3-4 weeks later boosted with VV, and 3-4 weeks later boosted again with purified protein in Freund's adjuvant.
• The vaccinia construct is a pSC11-based VV vector with the first 38 amino acids contributed by BH10 and the rest of gp120 and gp41 by the vaccine strain, the DNA construct is in the pJW4303 vector with a CMV promotor, and the purified protein is expressed from the pJW4303 vector transfected into CHO-K1 cells.
• Ten days after the final boost, hybridomas were made and tested for IL-2 production using either B6 spleen cells or H-2 IA^b transfected L cells as targets and Vβ usage was determined.
• Mice were immunized with an Env from either one of two clades: HIV-1 1007, a clade B strain isolated from an individual from Memphis Tennesee, and HIV-1 92UG005, a clade D vaccine isolated from Uganda in 1992 through the WHO.
• 80 unique clonotypes were characterized from six mice.
• H-2 IA^b restricted T-helper epitopes were concentrated in 5 distinct regions within the Env sequence (2 clonotype responses in V2, 26 in C2, 22 in V3, 23 in V4C4, and 7 in gp41).
• Epitope hotspots tended to be proximal to heavily glycosylated regions of the Env sequence, in exposed, non-helical strands of the protein. The non-uniform localization may be influenced by differential antigen processing and the glycosylation site proximity may allow binding to lectins and promote trafficking through processing pathways.

References

Surman2001 S. Surman, T. D. Lockey, K. S. Slobod, B. Jones, J. M. Riberdy, S. W. White, P. C. Doherty, and J. L. Hurwitz. Localization of CD4+ T Cell Epitope Hotspots to Exposed Strands of HIV Envelope Glycoprotein Suggests Structural Influences on Antigen Processing. Proc. Natl. Acad. Sci. U.S.A., 98(8):4587-4592, 10 Apr 2001. URL: http://www.pnas.org/cgi/content/full/98/8/4587. PubMed ID: 11287644. Show all entries for this paper.

Displaying record number 201355

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HXB2 Location	gp160(322-336) gp120(322-336) DNA(7188..7232)	gp160 Epitope Map
Author Location
Epitope	IIGDIRQAHCNISRE	Epitope Alignment
Subtype	B, D
Species (MHC/HLA)	mouse
Immunogen	vaccine
Experimental methods	Cytokine production
Keywords	epitope processing

Vaccine Details

Notes

• Murine hybridomas with known Env peptide specificities were tested for IL-2 production following stimulation with autologous splenocytes exposed to HIV-1-infected CXCR4 GHOST cells. Hybridomas were originally derived from C57BL/6 mice immunized with a prime-boost regimen. Antigen-processing potentials in the mouse system were studied.
• The presence of a target sequence within HIV-1 did not ensure T-cell reactivity. Subtype of immunogen used to elicit T-cell reactivity also did not predict T-cell responsiveness.
• IIGDIRQAHCNISRE was the target sequence for hybridoma 1007P3-11 and differed in 4 residues from HIV-1 pNL43 sequence infecting GHOST cells. The hybridoma did not have an IL-2 response to the HIV-1-infected CXCR4 GHOST cells.

References

Sealy2008 Robert Sealy, Wendy Chaka, Sherri Surman, Scott A. Brown, Peter Cresswell, and Julia L. Hurwitz. Target Peptide Sequence within Infectious Human Immunodeficiency Virus Type 1 Does Not Ensure Envelope-Specific T-Helper Cell Reactivation: Influences of Cysteine Protease and Gamma Interferon-Induced Thiol Reductase Activities. Clin. Vaccine Immunol., 15(4):713-719, Apr 2008. PubMed ID: 18235043. Show all entries for this paper.

Displaying record number 201397

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HXB2 Location	gp160(322-336) gp120(322-336) DNA(7188..7232)	gp160 Epitope Map
Author Location	gp120
Epitope	IIGDIRQAHCNISRE	Epitope Alignment
Subtype	A, B, C, D
Species (MHC/HLA)	mouse
Immunogen	vaccine
Country	United States
Experimental methods	Cytokine production
Keywords	subtype comparisons, immunodominance

Vaccine Details

Notes

• A vaccine study with B clade Envs in mice was unertaken to assess a subtype-specificity of responses. Four T-cell hybridomas responsive to subtype B envelope proteins were tested against 20 different subtype B envelope proteins and a protein each from subtypes A, C and D. IL-2 production was measured.
• No consistent correlation was found between T cell specificity towards epitopes from a certain (B) subtype or lack of specificity towards other (A, C, D) subtype.
• Not only did T-cell specificity not vary with subtype, but pairwise sequence comparisons of HIV gp120 envelope sequences showed that some US-derived sequences were more similar to sequences from distant countries than to each other
• Changes in core epitopes, flanking and distant regions, all affected responsiveness of the hybridomas to different subtype Env epitopes, showing that it is not only core changes that can eliminate T cell reactivity to an epitope.
• The above findings were substantiated by database analyses showing that epitope distributions are not necessarily dictated by subtype.
• Envelopes that shared residues 1-13 within this epitope (peptide IIGDIRQAHCNIS) were usually recognized by the hybridoma.

References

Brown2006 S. A. Brown, K. S. Slobod, S. Surman, A. Zirkel, X. Zhan, and J. L. Hurwitz. Individual HIV Type 1 Envelope-Specific T Cell Responses and Epitopes Do Not Segregate by Virus Subtype. AIDS Res. Hum. Retroviruses, 22(2):188-194, Feb 2006. PubMed ID: 16478402. Show all entries for this paper.