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Displaying record number 60666
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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 VGEIYKRWIIGLNK, VK-14, is from fragment CF2, was restricted by B*2705. There were no determinable natural processed epitope forms for subtypes B or C.
References
Tenzer2014
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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Displaying record number 52476
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- Comprehensive Elispot screening of 504 overlapping peptides that spanned all HIV-1 proteins in 57 HIV-1 infected individuals. Four groups of patients were compared: 23 were untreated; 12 patients were chronically infected and treated; 22 started treatment during acute infection, 11 continuously treated and 11 with STI.
- 63% of the peptides were recognized - the most frequent responses were directed against Nef (95%) and p24-Gag (88%). p17 was the most frequently recognized protein after correction for protein length. A median of 18 peptides (range 2-42) were recognized per person. The most frequently (>20%) recognized peptides were located in conserved regions within clade B sequences. Vpu was rarely recognized.
- A decrease in the total magnitude and in the breadth of CTL responses was detected in patients with treated acute infection in comparison to chronically infected treated or untreated individuals. No correlation between plasma viral load and HIV-1 specific T-cell responses was observed.
- The authors did not note the reference strain, but based on the peptide sequences provided it appears to be HXB2.
- Responses to this peptide were detected in 19% of the study subjects, and it was one of the 25 most frequently recognized peptides.
References
Addo2003
M. M. Addo, X. G. Yu, A. Rathod, D. Cohen, R. L. Eldridge, D. Strick, M. N. Johnston, C. Corcoran, A. G. Wurcel, C. A. Fitzpatrick, M. E. Feeney, W. R. Rodriguez, N. Basgoz, R. Draenert, David R. Stone, C. Brander, P. J. R. Goulder, E. S. Rosenberg, M. Altfeld, and B. D. Walker. Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load. J. Virol., 77(3):2081-2092, Feb 2003. PubMed ID: 12525643.
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