{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T19:02:07Z","timestamp":1761418927539,"version":"3.40.2"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Viral escape from HIV-1\u2013specific CD8+ T cells has been demonstrated in numerous studies previously. However, the qualitative features driving the emergence of mutations within epitopes are still unclear. In this study, we aimed to distinguish whether specific functional characteristics of HLA-B*5701\u2013restricted CD8+ T cells influence the emergence of mutations in high-risk progressors (HRPs) versus low-risk progressors (LRPs). Single-genome sequencing was performed to detect viral mutations (variants) within seven HLA-B*5701\u2013restricted epitopes in Gag (n = 4) and Nef (n = 3) in six untreated HLA-B*5701 subjects followed from early infection up to 7 y. Several well-characterized effector markers (IFN-\u03b3, IL-2, MIP-1\u03b2, TNF, CD107a, and perforin) were identified by flow cytometry following autologous (initial and emerging variant\/s) epitope stimulations. This study demonstrates that specific functional attributes may facilitate the outgrowth of mutations within HLA-B*5701\u2013restricted epitopes. A significantly lower fraction of IL-2\u2013producing cells and a decrease in functional avidity and polyfunctional sensitivity were evident in emerging epitope variants compared with the initial autologous epitopes. Interestingly, the HRPs mainly drove these differences, whereas the LRPs maintained a directed and maintained functional response against emerging epitope variants. In addition, LRPs induced improved cell-cycle progression and perforin upregulation after autologous and emerging epitope variant stimulations in contrast to HRPs. The maintained quantitative and qualitative features of the CD8+ T cell responses in LRPs toward emerging epitope variants provide insights into why HLA-B*5701 subjects have different risks of HIV-1 disease progression.<\/jats:p>","DOI":"10.4049\/jimmunol.1302253","type":"journal-article","created":{"date-parts":[[2014,4,17]],"date-time":"2014-04-17T06:47:46Z","timestamp":1397717266000},"page":"4685-4696","source":"Crossref","is-referenced-by-count":12,"title":["Functional Avidity and IL-2\/Perforin Production Is Linked to the Emergence of Mutations within HLA-B*5701\u2013Restricted Epitopes and HIV-1 Disease Progression"],"prefix":"10.1093","volume":"192","author":[{"given":"Marcus","family":"Buggert","sequence":"first","affiliation":[{"name":"Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet , Stockholm S-141 86,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa M","family":"Norstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet , Stockholm S-141 86,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Salemi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32611"},{"name":"Emerging Pathogens Institute, University of Florida , Gainesville, FL 32611"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick M","family":"Hecht","sequence":"additional","affiliation":[{"name":"University of California, San Francisco Positive Health Program, San Francisco General Hospital, University of California, San Francisco , San Francisco, CA 94110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika C","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet , Stockholm S-141 86,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,5,15]]},"reference":[{"key":"2025032404284444000_r1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/354453a0","article-title":"Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition","volume":"354","author":"Phillips","year":"1991","journal-title":"Nature"},{"key":"2025032404284444000_r2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/nm0297-212","article-title":"Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS","volume":"3","author":"Goulder","year":"1997","journal-title":"Nat. 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