{"id":322448,"date":"2016-11-15T19:05:09","date_gmt":"2016-11-16T03:05:09","guid":{"rendered":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/?post_type=msr-research-item&p=322448"},"modified":"2018-10-16T20:15:30","modified_gmt":"2018-10-17T03:15:30","slug":"targeting-cd8-t-cell-env-epitope-presented-hla-b5802-associated-markers-hiv-disease-progression-lack-selection-pressure","status":"publish","type":"msr-research-item","link":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/publication\/targeting-cd8-t-cell-env-epitope-presented-hla-b5802-associated-markers-hiv-disease-progression-lack-selection-pressure\/","title":{"rendered":"Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure"},"content":{"rendered":"

In HIV-infected persons, certain HLA class I alleles are associated with effective control of viremia, while others are associated with rapid disease progression. Among the most divergent clinical outcomes are the relatively good prognosis in HLA-B*5801 expressing persons and poor prognosis with HLA-B*5802. These two alleles differ by only three amino acids in regions involved in HLA-peptide recognition. This study evaluated a cohort of over 1000 persons with chronic HIV clade C virus infection to determine whether clinical outcome differences associated with B*5801 (n = 93) and B*5802 ( n = 259) expression are associated with differences in HIV-1-specific CD8 (+) T cell responses. The overall breadth and magnitude of HIV-1-specific CD8(+) T cell responses were lower in persons expressing B*5802, and epitope presentation by B*5802 contributed significantly less to the overall response as compared to B*5801-restricted CD8 (+) T cells. Moreover, viral load in B*5802-positive persons was higher and CD4 cell counts lower when this allele contributed to the overall CD8 (+) T cell response, which was detected exclusively through a single epitope in Env. In addition, persons heterozygous for B*5802 compared to persons homozygous for other HLA-B alleles had significantly higher viral loads. Viral sequencing revealed strong selection pressure mediated through B*5801-restricted responses but not through B*5802. These data indicate that minor differences in HLA sequence can have a major impact on epitope recognition, and that selective targeting of Env through HLA-B*5802 is at least ineffectual if not actively adverse in the containment of viremia. These results provide experimental evidence that not all epitope-specific responses contribute to immune containment, a better understanding of which is essential to shed light on mechanisms involved in HIV disease progression.<\/p>\n

\n
\n
<\/form>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

In HIV-infected persons, certain HLA class I alleles are associated with effective control of viremia, while others are associated with rapid disease progression. Among the most divergent clinical outcomes are the relatively good prognosis in HLA-B*5801 expressing persons and poor prognosis with HLA-B*5802. These two alleles differ by only three amino acids in regions involved […]<\/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":"","msr_editors":"","msr_how_published":"","msr_isbn":"","msr_issue":"1","msr_journal":"AIDS Res Hum Retroviruses","msr_number":"","msr_organization":"","msr_pages_string":"72-82","msr_page_range_start":"72","msr_page_range_end":"82","msr_series":"","msr_volume":"24","msr_copyright":"","msr_conference_name":"","msr_doi":"10.1089\/aid.2007.0124","msr_arxiv_id":"","msr_s2_paper_id":"","msr_mag_id":"","msr_pubmed_id":"","msr_other_authors":"","msr_other_contributors":"","msr_speaker":"","msr_award":"","msr_affiliation":"","msr_institution":"","msr_host":"","msr_version":"","msr_duration":"","msr_original_fields_of_study":"","msr_release_tracker_id":"","msr_s2_match_type":"","msr_citation_count_updated":"","msr_published_date":"2008-01-24","msr_highlight_text":"","msr_notes":"","msr_longbiography":"","msr_publicationurl":"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18275350","msr_external_url":"","msr_secondary_video_url":"","msr_conference_url":"","msr_journal_url":"","msr_s2_pdf_url":"","msr_year":0,"msr_citation_count":0,"msr_influential_citations":0,"msr_reference_count":0,"msr_s2_match_confidence":0,"msr_microsoftintellectualproperty":true,"msr_s2_open_access":false,"msr_s2_author_ids":[],"msr_pub_ids":[],"msr_hide_image_in_river":0,"footnotes":""},"msr-research-highlight":[],"research-area":[13553],"msr-publication-type":[193715],"msr-publisher":[],"msr-focus-area":[],"msr-locale":[268875],"msr-post-option":[],"msr-field-of-study":[],"msr-conference":[],"msr-journal":[],"msr-impact-theme":[],"msr-pillar":[],"class_list":["post-322448","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":"2008-01-24","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"72-82","msr_chapter":"","msr_isbn":"","msr_journal":"AIDS Res Hum Retroviruses","msr_volume":"24","msr_number":"","msr_editors":"","msr_series":"","msr_issue":"1","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":"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18275350","msr_doi":"10.1089\/aid.2007.0124","msr_publication_uploader":[{"type":"url","title":"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18275350","viewUrl":false,"id":false,"label_id":0},{"type":"doi","title":"10.1089\/aid.2007.0124","viewUrl":false,"id":false,"label_id":0}],"msr_related_uploader":"","msr_citation_count":0,"msr_citation_count_updated":"","msr_s2_paper_id":"","msr_influential_citations":0,"msr_reference_count":0,"msr_arxiv_id":"","msr_s2_author_ids":[],"msr_s2_open_access":false,"msr_s2_pdf_url":null,"msr_attachments":[{"id":0,"url":"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18275350"}],"msr-author-ordering":[{"type":"text","value":"KC Ngumbela","user_id":0,"rest_url":false},{"type":"text","value":"CL Day","user_id":0,"rest_url":false},{"type":"text","value":"Z Mncube","user_id":0,"rest_url":false},{"type":"text","value":"K Nair","user_id":0,"rest_url":false},{"type":"text","value":"D Ramduth","user_id":0,"rest_url":false},{"type":"text","value":"C Thobakgale","user_id":0,"rest_url":false},{"type":"text","value":"E Moodley","user_id":0,"rest_url":false},{"type":"text","value":"S Reddy","user_id":0,"rest_url":false},{"type":"text","value":"C de Pierres","user_id":0,"rest_url":false},{"type":"text","value":"N Mkhwanazi","user_id":0,"rest_url":false},{"type":"text","value":"K Bishop","user_id":0,"rest_url":false},{"type":"text","value":"M van der Stok","user_id":0,"rest_url":false},{"type":"text","value":"N Ismail","user_id":0,"rest_url":false},{"type":"text","value":"I honeyborne","user_id":0,"rest_url":false},{"type":"text","value":"H Crawford","user_id":0,"rest_url":false},{"type":"text","value":"DG Kavanagh","user_id":0,"rest_url":false},{"type":"text","value":"C Rousseau","user_id":0,"rest_url":false},{"type":"text","value":"D Nickle","user_id":0,"rest_url":false},{"type":"text","value":"J Mullins","user_id":0,"rest_url":false},{"type":"user_nicename","value":"heckerma","user_id":31991,"rest_url":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/microsoft-research\/v1\/researchers?person=heckerma"},{"type":"text","value":"B Korber","user_id":0,"rest_url":false},{"type":"text","value":"H Coovadia","user_id":0,"rest_url":false},{"type":"text","value":"P Kiepiela","user_id":0,"rest_url":false},{"type":"text","value":"PJ Goulder","user_id":0,"rest_url":false},{"type":"text","value":"BD Walker","user_id":0,"rest_url":false}],"msr_impact_theme":[],"msr_research_lab":[],"msr_event":[],"msr_group":[],"msr_project":[],"publication":[],"video":[],"msr-tool":[],"msr_publication_type":"article","related_content":[],"_links":{"self":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/322448","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item"}],"about":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/types\/msr-research-item"}],"version-history":[{"count":1,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/322448\/revisions"}],"predecessor-version":[{"id":524580,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/322448\/revisions\/524580"}],"wp:attachment":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/media?parent=322448"}],"wp:term":[{"taxonomy":"msr-research-highlight","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-highlight?post=322448"},{"taxonomy":"msr-research-area","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/research-area?post=322448"},{"taxonomy":"msr-publication-type","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-publication-type?post=322448"},{"taxonomy":"msr-publisher","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-publisher?post=322448"},{"taxonomy":"msr-focus-area","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-focus-area?post=322448"},{"taxonomy":"msr-locale","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-locale?post=322448"},{"taxonomy":"msr-post-option","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-post-option?post=322448"},{"taxonomy":"msr-field-of-study","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-field-of-study?post=322448"},{"taxonomy":"msr-conference","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-conference?post=322448"},{"taxonomy":"msr-journal","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-journal?post=322448"},{"taxonomy":"msr-impact-theme","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-impact-theme?post=322448"},{"taxonomy":"msr-pillar","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-pillar?post=322448"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}