{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:47:26Z","timestamp":1781110046708,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1995,4,25]]},"abstract":"<jats:p>Human T-cell leukemia virus type I (HTLV-I) gives rise to a neurologic disease known as HTLV-I-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP). Although the pathogenesis of the disease is unknown, the presence of a remarkably high frequency of Tax-specific, cytotoxic CD8 T cells may suggest a role of these cells in the development of HAM\/TSP. Antigen-mediated signaling in a CD8 T-cell clone specific for the Tax(11-19) peptide of HTLV-I was studied using analog peptides substituted in their T-cell receptor contact residues defined by x-ray crystallographic data of the Tax(11-19) peptide in the groove of HLA-A2. CD8 T-cell stimulation with the wild-type peptide antigen led to activation of p56lck kinase activity, interleukin 2 secretion, cytotoxicity, and clonal expansion. A Tax analog peptide with an alanine substitution of the T-cell receptor contact residue tyrosine-15 induced T-cell-mediated cytolysis without activation of interleukin 2 secretion or proliferation. Induction of p56lck kinase activity correlated with T-cell-mediated cytotoxicity, whereas interleukin 2 secretion correlated with [3H]thymidine incorporation and proliferation. Moreover, Tax peptide analogs that activated the tyrosine kinase activity of p56lck could induce unresponsiveness to secondary stimulation with the wild-type peptide. These observations show that a single amino acid substitution in a T-cell receptor contact residue of Tax can differentially signal CD8 T cells and further demonstrate that primary activation has functional consequences for the secondary response of at least some Tax-specific CD8 T cells to HTLV-I-infected target cells.<\/jats:p>","DOI":"10.1073\/pnas.92.9.4036","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:31:59Z","timestamp":1149067919000},"page":"4036-4040","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":32,"title":["Differential activation of proliferation and cytotoxicity in human T-cell lymphotropic virus type I Tax-specific CD8 T cells by an altered peptide ligand."],"prefix":"10.1073","volume":"92","author":[{"given":"P","family":"H\u00f6llsberg","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, Brigham &amp; Women's Hospital, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W E","family":"Weber","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Brigham &amp; Women's Hospital, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Dangond","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Brigham &amp; Women's Hospital, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Batra","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Brigham &amp; Women's Hospital, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Sette","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Brigham &amp; Women's Hospital, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D A","family":"Hafler","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Brigham &amp; Women's Hospital, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1995,4,25]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.92.9.4036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:59:48Z","timestamp":1649858388000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.92.9.4036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,4,25]]},"references-count":0,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1995,4,25]]}},"alternative-id":["10.1073\/pnas.92.9.4036"],"URL":"https:\/\/doi.org\/10.1073\/pnas.92.9.4036","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,4,25]]},"assertion":[{"value":"1995-04-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}