Search T Helper/CD4+ T-Cell Epitope Database

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Displaying record number 489

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HXB2 Location	gp160(405-420) gp120(405-420) DNA(7437..7484)	gp160 Epitope Map
Author Location	Env( 1007)
Epitope	`SNNTVGNPIILPCRI`	Epitope Alignment
Species (MHC/HLA)	mouse(H-2 IA^b)
Immunogen	vaccine
Experimental methods
Keywords	subtype comparisons, epitope processing, TCR usage

Vaccine Details

Vaccine type	DNA, protein, vaccinia
Vaccine strain	B clade 1007, D clade UG92005
Vaccine component	gp140
Adjuvant	Complete Freund's Adjuvant (CFA)

Notes

This epitope is located in the V4C4 region of 1007 (US, clade B) and was recognized by 13 hybridomas with Vβ usage Vβ 4, 7, 8.1, 8.2, 10, 12 and not determined -- one of the Vβ 8.2 was shown to utilize Vα 2.
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 200980

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HXB2 Location	gp160(405-420) gp120(405-420) DNA(7437..7484)	gp160 Epitope Map
Author Location	Env (gp160)( 1007)
Epitope	`SNNTVGNPIILPCRI`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	mouse(H-2^b)
Immunogen	vaccine
Experimental methods	CD4 T-cell Elispot - IFNγ, Cytokine production
Keywords	vaccine-induced immune responses, variant cross-reactivity, vaccine antigen design

Vaccine Details

Vaccine type	DNA, protein, vaccinia
Vaccine strain	B clade 1007, D clade UG92005
Vaccine component	Env
Adjuvant	Complete Freund's Adjuvant (CFA)

Notes

To develop a polyvalent Env vaccine, subtype specific B and D T-helper epitopes were identified, and mixtures of strain 1007, clade B, or UG92005, clade D envelopes were given to C57BL/6J mice. Mice were intramuscularly immunized with recombinant DNA, then intraperitoneally with rVV and finally with env protein in CFA. A dilution of 1/100 could still elicit type specific responses, and responses persisted with different prime boost combinations.
T-cell hybridoma 1007P3-23 was isolated from mice immunized with 1007, and it recognized the peptide SNNTVGNPIILPCRI of the V4/C4 region. The minimal, core peptide recognized by 10007P3-23 was NPIIL, a sequence not found in UG92005, which has a deletion in the core, so that the equivalent region in the D isolate is NNET---ITLQCRI
Priming mixtures of 1007 and UG92005 induced both Env-specific (SNNTVGNPIILPCRI and AMYAPPIAGLIQCSS) and cross-reactive (PKVSFEPIPIHYCAP, C2, GNIRQAHCNVSKAKW, V3-C3) Th responses in murine spleen cells.

References

Zhan2004 Xiaoyan Zhan, Karen S. Slobod, Sherri Surman, Scott A. Brown, Chris Coleclough, and Julia L. Hurwitz. Minor cOmponents of a Multi-Envelope HIV Vaccine are Recognized by Type-Specific T-Helper Cells. Vaccine, 22(9-10):1206-1213, 12 Mar 2004. PubMed ID: 15003649. Show all entries for this paper.