The strongest genetic influence on immune control in HIV-1 infection is the HLA class I genotype. Rapid disease progression in B-clade infection has been linked to HLA-B*35 expression, in particular to the less common HLA-B*3502 and HLA-B*3503 subtypes but also to the most prevalent subtype, HLA-B*3501. In these studies we first demonstrated that whereas HLA-B*3501 is associated with a high viral set point in two further B-clade-infected cohorts, in Japan and Mexico, this association does not hold in two large C-clade-infected African cohorts. We tested the hypothesis that clade-specific differences in HLA associations with disease outcomes may be related to distinct targeting of critical CD8+ T-cell epitopes. We observed that only one epitope was significantly targeted differentially, namely, the Gag-specific epitope NPPIPVGDIY (NY10, Gag positions 253 to 262) (P = 2 \u00d7 10\u22125). In common with two other HLA-B*3501-restricted epitopes, in Gag and Nef, that were not targeted differentially, a response toward NY10 was associated with a significantly lower viral set point. Nonimmunogenicity of NY10 in B-clade-infected subjects derives from the Gag-D260E polymorphism present in \u223c90% of B-clade sequences, which critically reduces recognition of the Gag NY10 epitope. These data suggest that in spite of any inherent HLA-linked T-cell receptor repertoire differences that may exist, maximizing the breadth of the Gag-specific CD8+ T-cell response, by the addition of even a single epitope, may be of overriding importance in achieving immune control of HIV infection. This distinction is of direct relevance to development of vaccines designed to optimize the anti-HIV CD8+ T-cell response in all individuals, irrespective of HLA type. <\/p>\n","protected":false},"excerpt":{"rendered":"
The strongest genetic influence on immune control in HIV-1 infection is the HLA class I genotype. Rapid disease progression in B-clade infection has been linked to HLA-B*35 expression, in particular to the less common HLA-B*3502 and HLA-B*3503 subtypes but also to the most prevalent subtype, HLA-B*3501. In these studies we first demonstrated that whereas HLA-B*3501 […]<\/p>\n","protected":false},"featured_media":0,"template":"","meta":{"msr-url-field":"","msr-podcast-episode":"","msrModifiedDate":"","msrModifiedDateEnabled":false,"ep_exclude_from_search":false,"footnotes":""},"msr-content-type":[3],"msr-research-highlight":[],"research-area":[13553],"msr-publication-type":[193715],"msr-product-type":[],"msr-focus-area":[],"msr-platform":[],"msr-download-source":[],"msr-locale":[268875],"msr-field-of-study":[],"msr-conference":[],"msr-journal":[],"msr-impact-theme":[],"msr-pillar":[],"class_list":["post-322988","msr-research-item","type-msr-research-item","status-publish","hentry","msr-research-area-medical-health-genomics","msr-locale-en_us"],"msr_publishername":"","msr_edition":"","msr_affiliation":"","msr_published_date":"2012-12-04","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"12643-12654","msr_chapter":"","msr_isbn":"","msr_journal":"Journal of Virololgy","msr_volume":"86","msr_number":"","msr_editors":"","msr_series":"","msr_issue":"23","msr_organization":"","msr_how_published":"","msr_notes":"","msr_highlight_text":"","msr_release_tracker_id":"","msr_original_fields_of_study":"","msr_download_urls":"","msr_external_url":"","msr_secondary_video_url":"","msr_longbiography":"","msr_microsoftintellectualproperty":1,"msr_main_download":"","msr_publicationurl":"http:\/\/jvi.asm.org\/content\/86\/23\/12643.long","msr_doi":"10.1128\/JVI.01381-12","msr_publication_uploader":[{"type":"url","title":"http:\/\/jvi.asm.org\/content\/86\/23\/12643.long","viewUrl":false,"id":false,"label_id":0},{"type":"doi","title":"10.1128\/JVI.01381-12","viewUrl":false,"id":false,"label_id":0}],"msr_related_uploader":"","msr_attachments":[{"id":0,"url":"http:\/\/jvi.asm.org\/content\/86\/23\/12643.long"}],"msr-author-ordering":[{"type":"text","value":"Philippa C. Matthews","user_id":0,"rest_url":false},{"type":"text","value":"Madoka Koyanagi","user_id":0,"rest_url":false},{"type":"text","value":"Henrik N. Kloverpris","user_id":0,"rest_url":false},{"type":"text","value":"Mikkel Harndahl","user_id":0,"rest_url":false},{"type":"text","value":"Anette Stryhn","user_id":0,"rest_url":false},{"type":"text","value":"Tomohiro Akahoshi","user_id":0,"rest_url":false},{"type":"text","value":"Hiroyuki Gatanaga","user_id":0,"rest_url":false},{"type":"text","value":"Shinichi Oka","user_id":0,"rest_url":false},{"type":"text","value":"Claudia Juarez Molina","user_id":0,"rest_url":false},{"type":"text","value":"Humberto Valenzuela Ponce","user_id":0,"rest_url":false},{"type":"text","value":"Santiago Avila Rios","user_id":0,"rest_url":false},{"type":"text","value":"David Cole","user_id":0,"rest_url":false},{"type":"user_nicename","value":"carlson","user_id":31333,"rest_url":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/microsoft-research\/v1\/researchers?person=carlson"},{"type":"text","value":"Rebecca P. Payne","user_id":0,"rest_url":false},{"type":"text","value":"Anthony Ogwu","user_id":0,"rest_url":false},{"type":"text","value":"Alfred Bere","user_id":0,"rest_url":false},{"type":"text","value":"Thumbi Ndung'u","user_id":0,"rest_url":false},{"type":"text","value":"Kamini Gounder","user_id":0,"rest_url":false},{"type":"text","value":"Fabian Chen","user_id":0,"rest_url":false},{"type":"text","value":"Lynn Riddell","user_id":0,"rest_url":false},{"type":"text","value":"Graz Luzzi","user_id":0,"rest_url":false},{"type":"text","value":"Roger Shaprio","user_id":0,"rest_url":false},{"type":"text","value":"Christian Brander","user_id":0,"rest_url":false},{"type":"text","value":"Bruce Walker","user_id":0,"rest_url":false},{"type":"text","value":"Andrew K. sewell","user_id":0,"rest_url":false},{"type":"text","value":"Gustavo Reyes Teran","user_id":0,"rest_url":false},{"type":"user_nicename","value":"heckerma","user_id":31991,"rest_url":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/microsoft-research\/v1\/researchers?person=heckerma"},{"type":"text","value":"Eric Hunter","user_id":0,"rest_url":false},{"type":"text","value":"Soren Buus","user_id":0,"rest_url":false},{"type":"text","value":"Masafumi Takiguchi","user_id":0,"rest_url":false},{"type":"text","value":"Philip J.R. Goulder","user_id":0,"rest_url":false}],"msr_impact_theme":[],"msr_research_lab":[],"msr_event":[],"msr_group":[],"msr_project":[],"publication":[],"video":[],"download":[],"msr_publication_type":"article","_links":{"self":[{"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/322988"}],"collection":[{"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item"}],"about":[{"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/types\/msr-research-item"}],"version-history":[{"count":1,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/322988\/revisions"}],"predecessor-version":[{"id":525174,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/322988\/revisions\/525174"}],"wp:attachment":[{"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/media?parent=322988"}],"wp:term":[{"taxonomy":"msr-content-type","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-content-type?post=322988"},{"taxonomy":"msr-research-highlight","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-research-highlight?post=322988"},{"taxonomy":"msr-research-area","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/research-area?post=322988"},{"taxonomy":"msr-publication-type","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-publication-type?post=322988"},{"taxonomy":"msr-product-type","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-product-type?post=322988"},{"taxonomy":"msr-focus-area","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-focus-area?post=322988"},{"taxonomy":"msr-platform","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-platform?post=322988"},{"taxonomy":"msr-download-source","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-download-source?post=322988"},{"taxonomy":"msr-locale","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-locale?post=322988"},{"taxonomy":"msr-field-of-study","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-field-of-study?post=322988"},{"taxonomy":"msr-conference","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-conference?post=322988"},{"taxonomy":"msr-journal","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-journal?post=322988"},{"taxonomy":"msr-impact-theme","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-impact-theme?post=322988"},{"taxonomy":"msr-pillar","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-pillar?post=322988"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}