{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T02:53:24Z","timestamp":1778900004609,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T00:00:00Z","timestamp":1719014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid from the Ministry of Health, Labour, and Welfare of Japan","award":["21fk0108124h2102"],"award-info":[{"award-number":["21fk0108124h2102"]}]},{"name":"Grant-in-Aid from the Ministry of Health, Labour, and Welfare of Japan","award":["19K07999"],"award-info":[{"award-number":["19K07999"]}]},{"name":"Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["21fk0108124h2102"],"award-info":[{"award-number":["21fk0108124h2102"]}]},{"name":"Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["19K07999"],"award-info":[{"award-number":["19K07999"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Increased human T-cell leukemia virus type 1 (HTLV-1) proviral load (PVL) is a significant risk factor for HTLV-1-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP). There is controversy surrounding whether HTLV-1-specific cytotoxic T lymphocytes (CTLs) are beneficial or harmful to HAM\/TSP patients. Recently, HTLV-1 Tax 301\u2013309 has been identified as an immunodominant epitope restricted to HLA-A*2402. We investigated whether HLA-A*24 reduces HTLV-1 PVL and the risk of HAM\/TSP using blood samples from 152 HAM\/TSP patients and 155 asymptomatic HTLV-1 carriers. The allele frequency of HLA-A*24 was higher in HAM\/TSP patients than in asymptomatic HTLV-1 carriers (72.4% vs. 58.7%, odds ratio 1.84), and HLA-A*24-positive patients showed a 42% reduction in HTLV-1 PVL compared to negative patients. Furthermore, the PVL negatively correlated with the frequency of Tax 301\u2013309-specific CTLs. These findings are opposite to the effects of HLA-A*02, which reduces HTLV-1 PVL and the risk of HAM\/TSP. Therefore, we compared the functions of CTLs specific to Tax 11\u201319 or Tax 301\u2013309, which are immunodominant epitopes restricted to HLA-A*0201 or HLA-A*2402, respectively. The maximum responses of these CTLs were not different in the production of IFN-\u03b3 and MIP-1\u03b2 or in the expression of CD107a\u2014a marker for the degranulation of cytotoxic molecules. However, Tax 301\u2013309-specific CTLs demonstrated 50-fold higher T-cell avidity than Tax 11\u201319-specific CTLs, suggesting better antigen recognition at low expression levels of the antigens. These findings suggest that HLA-A*24, which induces sensitive HTLV-1-specific CTLs, increases the risk of HAM\/TSP despite reducing HTLV-1 PVL.<\/jats:p>","DOI":"10.3390\/ijms25136858","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T08:42:03Z","timestamp":1719218523000},"page":"6858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["HLA-A*24 Increases the Risk of HTLV-1-Associated Myelopathy despite Reducing HTLV-1 Proviral Load"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4098-385X","authenticated-orcid":false,"given":"Masakazu","family":"Tanaka","sequence":"first","affiliation":[{"name":"Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norihiro","family":"Takenouchi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1010, Japan"},{"name":"Department of Neurology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiho","family":"Arishima","sequence":"additional","affiliation":[{"name":"Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshio","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4909-7769","authenticated-orcid":false,"given":"Satoshi","family":"Nozuma","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8215-8853","authenticated-orcid":false,"given":"Eiji","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Takashima","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuji","family":"Kubota","sequence":"additional","affiliation":[{"name":"Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5682","DOI":"10.1128\/jvi.64.11.5682-5687.1990","article-title":"In vivo cellular tropism of human T-cell leukemia virus type 1","volume":"64","author":"Richardson","year":"1990","journal-title":"J. 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