{"id":343115,"date":"2016-12-29T11:52:02","date_gmt":"2016-12-29T19:52:02","guid":{"rendered":"https:\/\/www.microsoft.com\/en-us\/research\/?post_type=msr-research-item&p=343115"},"modified":"2018-10-16T21:35:34","modified_gmt":"2018-10-17T04:35:34","slug":"enhanced-recognition-hiv-1-cryptic-epitopes-restricted-hla-class-alleles-associated-favorable-clinical-outcome","status":"publish","type":"msr-research-item","link":"https:\/\/www.microsoft.com\/en-us\/research\/publication\/enhanced-recognition-hiv-1-cryptic-epitopes-restricted-hla-class-alleles-associated-favorable-clinical-outcome\/","title":{"rendered":"Enhanced Recognition of HIV-1 Cryptic Epitopes Restricted by HLA Class I Alleles Associated With a Favorable Clinical Outcome."},"content":{"rendered":"
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Cryptic epitopes (CEs) are peptides derived from the translation of 1 or more of the 5 alternative reading frames (ARFs; 2 sense and 3 antisense) of genes. Here, we compared response rates to HIV-1-specific CE predicted to be restricted by HLA-I alleles associated with protection against disease progression to those without any such association.Peptides (9mer to 11mer) were designed based on HLA-I-binding algorithms for B*27, B*57, or B*5801 (protective alleles) and HLA-B*5301 or B*5501 (nonprotective allele) in all 5 ARFs of the 9 HIV-1 encoded proteins. Peptides with >50% probability of being an epitope (n = 231) were tested for T-cell responses in an IFN-γ enzyme-linked immunosorbent spot (ELISpot) assay. Peripheral blood mononuclear cell samples from HIV-1 seronegative donors (n = 42) and HIV-1 seropositive patients with chronic clade B infections (n = 129) were used.Overall, 16%, 2%, and 2% of chronic HIV infected patients had CE responses by IFN-γ ELISpot in the protective, nonprotective, and seronegative groups, respectively (P = 0.009, Fischer exact test). Twenty novel CE-specific responses were mapped (median magnitude of 95 spot forming cells\/10 peripheral blood mononuclear cells), and most were both antisense derived (90%) and represented ARFs of accessory proteins (55%). CE-specific CD8 T cells were multifunctional and proliferated when assessed by intracellular cytokine staining.CE responses were preferentially restricted by the protective HLA-I alleles in HIV-1 infection, suggesting that they may contribute to viral control in this group of patients.<\/div>\n<\/div>\n<\/div>\n
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Cryptic epitopes (CEs) are peptides derived from the translation of 1 or more of the 5 alternative reading frames (ARFs; 2 sense and 3 antisense) of genes. Here, we compared response rates to HIV-1-specific CE predicted to be restricted by HLA-I alleles associated with protection against disease progression to those without any such association.Peptides (9mer […]<\/p>\n","protected":false},"featured_media":0,"template":"","meta":{"msr-url-field":"","msr-podcast-episode":"","msrModifiedDate":"","msrModifiedDateEnabled":false,"ep_exclude_from_search":false,"_classifai_error":"","msr-author-ordering":null,"msr_publishername":"","msr_publisher_other":"","msr_booktitle":"","msr_chapter":"","msr_edition":"Journal of Acquired Immune Deficiency Syndromes","msr_editors":"","msr_how_published":"","msr_isbn":"","msr_issue":"","msr_journal":"Journal of Acquired Immune Deficiency 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