Search CTL/CD8+ T-Cell Epitope Database

Found 2 matching records:

Displaying record number 58703

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HXB2 Location	Gag(385-393) p2p7p1p6(22-30) DNA(1942..1968)	Gag Epitope Map
Author Location	p24(385-393)
Epitope	`GPKRIVKCF`	Epitope Alignment
Epitope Name	p24-GF9
Subtype	C
Species (MHC/HLA)	human(B*42:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A30:01, B42:01, C*17:01
Country	Botswana, South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HLA associated polymorphism

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.
An 18-mer peptide containing p24-Gag epitope GF9, GPKRIVKCF, was recognized only by B*4201-positive subjects versus 0% of HLA-B*4202 carriers. It is a novel C-clade epitope restricted by HLA-B*4201.

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 59434

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HXB2 Location	Gag(385-393) p2p7p1p6(22-30) DNA(1942..1968)	Gag Epitope Map
Author Location	Gag(386-394)
Epitope	`GPKRIVKCF`	Epitope Alignment
		Show epitope variants
Epitope Name	Gag-GF9
Subtype	C
Species (MHC/HLA)	human(B*42:01)
Immunogen	HIV-1 infection
Country	Botswana, South Africa, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Other, Tetramer binding
Keywords	immunodominance, escape, novel epitope

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.
Novel epitope GPKRIVKCF from OLP Gag-52 (QRSNFKGPKRIVKCF) had a targeting frequency of ˜4% of 154 HLA-B*4201⁺ subjects. Immunodominance rank was 16/20 tested epitopes. Gag GF9-specific responses trend with lower median viral loads (VL).
Gag-GF9-HLA-B*4202's binding affinity, K_d = 8 nM; stability, K_1/2 = 11h.
2 polymorphisms were selected by HLA-B*4201 in this Gag-GF9 epitope, P386S and K387R.

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.