{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:23:31Z","timestamp":1785425011515,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,7]]},"group-title":"Immunology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["DP2AI154421"],"award-info":[{"award-number":["DP2AI154421"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UM1AI154560"],"award-info":[{"award-number":["UM1AI154560"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Gates Foundation","award":["INV-008696"],"award-info":[{"award-number":["INV-008696"]}]},{"name":"Gates Foundation","award":["INV-064567"],"award-info":[{"award-number":["INV-064567"]}]},{"award":["Career Award for Medical Scientists"],"award-info":[{"award-number":["Career Award for Medical Scientists"]}],"id":[{"id":"https:\/\/ror.org\/01d35cw23","id-type":"ROR","asserted-by":"publisher"}]},{"award":["HIV Scholars Award"],"award-info":[{"award-number":["HIV Scholars Award"]}],"id":[{"id":"https:\/\/ror.org\/056546b03","id-type":"ROR","asserted-by":"publisher"}]},{"name":"MGH Executive Committee on Research","award":["Howard Goodman Fellowship"],"award-info":[{"award-number":["Howard Goodman Fellowship"]}]},{"name":"MGH Executive Committee on Research","award":["Giammaria and Sabrina Giuliani MGB Research Scholars Award"],"award-info":[{"award-number":["Giammaria and Sabrina Giuliani MGB Research Scholars Award"]}]},{"DOI":"10.13039\/501100004052","name":"KAUST","doi-asserted-by":"crossref","award":["Ibn Rushd Postdoctoral Fellowship"],"award-info":[{"award-number":["Ibn Rushd Postdoctoral Fellowship"]}],"id":[{"id":"10.13039\/501100004052","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Durable treatment-free remission remains a defining goal for people living with HIV (PLWH). Studies of spontaneous elite controllers have revealed that functional CD8\u207a T cells targeting structurally networked viral epitopes can mediate durable viral suppression\n                  <jats:sup>1,2<\/jats:sup>\n                  . However, rare reservoir-defined exceptional controllers within the spectrum of elite control\n                  <jats:sup>3\u20135<\/jats:sup>\n                  , characterized by the absence of intact provirus or proviruses confined to transcriptionally repressed genomic regions\n                  <jats:sup>6<\/jats:sup>\n                  , provide a unique opportunity to define mechanisms of cure-like immunity. Here, we integrate functional epitope mapping, single-cell transcriptomics, and infected cell elimination assays to identify networked HIV epitope targeting and a natural killer (NK)-like killer-cell immunoglobulin-like receptor (KIR)\u207a CD8\u207a T cell subset as key features of exceptional control. This NK-like subset was selectively enriched within HIV-specific, but not CMV-specific, CD8\u207a T cells from controllers, and was transcriptionally similar to highly cytotoxic subsets within the broader KIR\n                  <jats:sup>+<\/jats:sup>\n                  CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell compartment. Flow cytometry revealed increased frequencies of KIR\u207a CD8\u207a T cells in exceptional controllers relative to antiretroviral therapy (ART)-suppressed individuals, and unexpectedly, enrichment of dual KIR\n                  <jats:sup>+<\/jats:sup>\n                  NKG2A\n                  <jats:sup>+<\/jats:sup>\n                  CD8\u207a T cells. Functional depletion of KIR\u207a CD8\u207a T cells significantly impaired the elimination of autologous HIV-infected CD4\u207a T cells, despite preserved recognition by proliferative networked HIV-specific CD8\u207a T cells. These findings thereby identify an NK-like KIR\u207a CD8\u207a T cell state as a previously unrecognized component of exceptional HIV immunity that complements networked epitope targeting, providing a novel framework for immunotherapeutic HIV cure strategies.\n                <\/jats:p>","DOI":"10.64898\/2026.07.02.735504","type":"posted-content","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:35:11Z","timestamp":1783488911000},"source":"Crossref","is-referenced-by-count":0,"title":["NK-like and networked CD8\n                  <sup>+<\/sup>\n                  T cell immunity mediates exceptional HIV control"],"prefix":"10.64898","author":[{"given":"Aljawharah","family":"Alrubayyi","sequence":"first","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Traunbauer","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Crain","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaown","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Collins","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsinyen","family":"Huang","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarety","family":"Kaseke","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umar","family":"Arshad","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Lian","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarthi","family":"Vijayakumar","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"},{"name":"Program in Health Sciences and Technology, Harvard Medical School, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Getz","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Lichterfeld","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"},{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu G.","family":"Yu","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Walker","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD, USA"},{"name":"Institute of Medical Engineering and Science and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg M.","family":"Lauer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA"},{"name":"Broad Institute, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6875-4472","authenticated-orcid":false,"given":"Gaurav D.","family":"Gaiha","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA"},{"name":"Program in Health Sciences and Technology, Harvard Medical School, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, 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