{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T04:19:37Z","timestamp":1772857177062,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"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":[[2018,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Unlike cytosolic processing and presentation of viral Ags by virus-infected cells, Ags first expressed in infected nonprofessional APCs, such as CD4+ T cells in the case of HIV, are taken up by dendritic cells and cross-presented. This generally requires entry through the endocytic pathway, where endosomal proteases have first access for processing. Thus, understanding virus escape during cross-presentation requires an understanding of resistance to endosomal proteases, such as cathepsin S (CatS). We have modified HIV-1MN gp120 by mutating a key CatS cleavage site (Thr322Thr323) in the V3 loop of the immunodominant epitope IGPGRAFYTT to IGPGRAFYVV to prevent digestion. We found this mutation to facilitate cross-presentation and provide evidence from MHC binding and X-ray crystallographic structural studies that this results from preservation of the epitope rather than an increased epitope affinity for the MHC class I molecule. In contrast, when the protein is expressed by a vaccinia virus in the cytosol, the wild-type protein is immunogenic without this mutation. These proof-of-concept results show that a virus like HIV, infecting predominantly nonprofessional presenting cells, can escape T cell recognition by incorporating a CatS cleavage site that leads to destruction of an immunodominant epitope when the Ag undergoes endosomal cross-presentation.<\/jats:p>","DOI":"10.4049\/jimmunol.1701523","type":"journal-article","created":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T15:50:15Z","timestamp":1516981815000},"page":"1853-1864","source":"Crossref","is-referenced-by-count":16,"title":["Effects of Cross-Presentation, Antigen Processing, and Peptide Binding in HIV Evasion of T Cell Immunity"],"prefix":"10.1093","volume":"200","author":[{"given":"Blake F","family":"Frey","sequence":"first","affiliation":[{"name":"Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0964-5481","authenticated-orcid":false,"given":"Jiansheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1568-4607","authenticated-orcid":false,"given":"Yongjun","family":"Sui","sequence":"additional","affiliation":[{"name":"Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5126-6250","authenticated-orcid":false,"given":"Lisa F","family":"Boyd","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3705-0453","authenticated-orcid":false,"given":"Bin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Engineering, University of California , Santa Cruz, Santa Cruz, CA 95064"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwen","family":"Tatsuno","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Engineering, University of California , Santa Cruz, Santa Cruz, CA 95064"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4533-7304","authenticated-orcid":false,"given":"Rolf","family":"Billeskov","sequence":"additional","affiliation":[{"name":"Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahram","family":"Solaymani-Mohammadi","sequence":"additional","affiliation":[{"name":"Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip W","family":"Berman","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Engineering, University of California , Santa Cruz, Santa Cruz, CA 95064"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8530-7375","authenticated-orcid":false,"given":"David H","family":"Margulies","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay A","family":"Berzofsky","sequence":"additional","affiliation":[{"name":"Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,3,1]]},"reference":[{"key":"2025030610052685000_r1"},{"key":"2025030610052685000_r2"},{"key":"2025030610052685000_r3","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1056\/NEJMoa1113425","article-title":"Immune-correlates analysis of an HIV-1 vaccine efficacy trial","volume":"366","author":"Haynes","year":"2012","journal-title":"N. 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