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- Subtype-specific substitutions in two HIV Gag regions (fragments F1, amino acids (aa) 5-46, and F2 aa 100-143) result in novel adaptations that affect epitope processing efficiency. Consequent low epitope abundance is associated with weak T cell response and greater immune escape and therefore with disease state. Conversely, epitopes from these regions when restricted by certain rare HLA I alleles, are associated with greater production and resulting CTL response, therefore delayed disease progression.
- Most epitopes were found to be processed as precursors with N-terminal extensions beyond the optimal epitope. Only 4 epitopes in this region were associated with delayed progression - HLA-B*5701/03-restricted IW9 (ISPRTLNAW), KF11 (KAFSPEVIPMF), TW10 (TSTLQEQIGW) and HLA-B*2705-restricted KK10 (KRWIILGLNK).
- Regardless of ethnic group, white or African, a significant three-way interaction was found between HLA allelic frequency, epitope yield and ethnicity for epitopes of N-terminal fragment F1 (NF1) and C-terminal as well as middle F2 (CF2 and MF2). C-terminal F1 (CF1) epitope yields however, showed a significant difference between ethnic groups. Also, for identical HLA-mediated selection pressure in both Africans and whites, HIV-C had a lower concentration than HIV-B, especially at lower HLA allelic frequencies.
- Epitope KRWIILGLNKIVR, KR-13, from fragment NF2-MF2, restrictied by HLA-A*03, A*11, A*33, B*2705, (Tenzer, S et al, Nature Immunology 2009), had no determined natural processed epitope forms for subtypes B or C. When studied from CF2 as the - KK10 peptide form, (Tenzer, S et al, Nature Immunology 2009), natural processed epitope forms for subtype B were NNPPIPVGEIYKRWIILGLNKIVR (proline 122,123, 125), NPPIPVGEIYKRWIILGLNKIVR (proline 122,123, 125), RWIILGLNKIVR , with respective %s of 0, 0, 100 after 4 hours processing through constitutive proteasomes, and %s of 46, 52, 2 after 4h through immuno proteasomes respectively. For subtype C, natural processed forms were KRWIILGLNKIVR, RWIILGLNKIVR, with %s from 4h post constitutive proteasome being 75, 25 and %s after processing 4h through immuno proteasomes being 98, 2 respectively.
Stefan Tenzer, Hayley Crawford, Phillip Pymm, Robert Gifford, Vattipally B. Sreenu, Mirjana Weimershaus, Tulio de Oliveira, Anne Burgevin, Jan Gerstoft, Nadja Akkad, Daniel Lunn, Lars Fugger, John Bell, Hansjörg Schild, Peter van Endert, and Astrid K. N. Iversen. HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification. Cell Rep., 7(2):448-463, 24 Apr 2014. PubMed ID: 24726370.
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