{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:53:51Z","timestamp":1774947231320,"version":"3.50.1"},"reference-count":37,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human T-lymphotropic virus type 1 (HTLV-1)\u2013associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) is an inflammatory neurologic disease caused by HTLV-1 infection, in which HTLV-1\u2013infected CD4+ T cells and HTLV-1\u2013specific CD8+ T cells may play a role in the disease pathogenesis. Patients with HAM\/TSP have high proviral loads despite vigorous virus-specific CD8+ T-cell responses; however, it is unknown whether the T cells are efficient in eliminating the virus in vivo. To define the dynamics of HTLV-1\u2013specific CD8+T-cell responses, we investigated longitudinal alterations in HTLV-1 proviral load, amino acid changes in an immunodominant viral epitope, frequency of HTLV-1\u2013specific T cells, and degeneracy of T-cell recognition in patients with HAM\/TSP. We showed that the frequency and the degeneracy of the HTLV-1\u2013specific CD8+ T cells correlated well with proviral load in the longitudinal study. The proviral load was much higher in a patient with low degeneracy of HTLV-1\u2013specific T cells compared to that in a patient with comparable frequency but higher degeneracy of the T cells. Furthermore, in a larger number of patients divided into 2 groups by the proviral load, those with high proviral load had lower degeneracy of T-cell recognition than those with low proviral load. Sequencing analysis revealed that epitope mutations were remarkably increased in a patient when the frequency and the degeneracy were at the lowest. These data suggest that HTLV-1\u2013specific CD8+ T cells with degenerate specificity are increased during viral replication and control the viral infection.<\/jats:p>","DOI":"10.1182\/blood-2002-08-2477","type":"journal-article","created":{"date-parts":[[2003,4,2]],"date-time":"2003-04-02T18:43:59Z","timestamp":1049309039000},"page":"3074-3081","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":28,"title":["Degenerate specificity of HTLV-1\u2013specific CD8+ T cells during viral replication in patients with HTLV-1\u2013associated myelopathy (HAM\/TSP)"],"prefix":"10.1182","volume":"101","author":[{"given":"Ryuji","family":"Kubota","sequence":"first","affiliation":[{"name":"From the Third Department of Internal Medicine, Center for Chronic Viral Diseases, and Department of Medical Informatics, Faculty of Medicine, Kagoshima University, Kagoshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Furukawa","sequence":"additional","affiliation":[{"name":"From the Third Department of Internal Medicine, Center for Chronic Viral Diseases, and Department of Medical Informatics, Faculty of Medicine, Kagoshima University, Kagoshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Izumo","sequence":"additional","affiliation":[{"name":"From the Third Department of Internal Medicine, Center for Chronic Viral Diseases, and Department of Medical Informatics, Faculty of Medicine, Kagoshima University, Kagoshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichiro","family":"Usuku","sequence":"additional","affiliation":[{"name":"From the Third Department of Internal Medicine, Center for Chronic Viral Diseases, and Department of Medical Informatics, Faculty of Medicine, Kagoshima University, Kagoshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuhiro","family":"Osame","sequence":"additional","affiliation":[{"name":"From the Third Department of Internal Medicine, Center for Chronic Viral Diseases, and Department of Medical Informatics, Faculty of Medicine, Kagoshima University, Kagoshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2019111617311817000_B1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/248701a0","article-title":"Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system.","volume":"248","author":"Zinkernagel","year":"1974","journal-title":"Nature."},{"key":"2019111617311817000_B2","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/0092-8674(86)90019-X","article-title":"The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic 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