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Recently, <jats:italic>HLA-DQA1*05:03<\/jats:italic> was shown to be significantly associated with NMOSD in a Japanese patient cohort. However, the specific mechanism by which <jats:italic>HLA-DQA1*05:03<\/jats:italic> is associated with the development of NMOSD has yet to be elucidated. In the current study, we revealed that <jats:italic>HLA-DQA1*05:03<\/jats:italic> exhibited significantly higher cell surface expression levels compared to other various <jats:italic>DQA1<\/jats:italic> alleles, and that its expression strongly depended on the amino acid sequence of the \u03b11 domain, with a preference for leucine at position 75. Moreover, in silico analysis indicated that the HLA-DQ encoded by <jats:italic>HLA-DQA1*05:03<\/jats:italic> preferentially presents immunodominant AQP4 peptides, and that the peptide major histocompatibility complexes (pMHCs) are more energetically stable in the presence of <jats:italic>HLA-DQA1*05:03<\/jats:italic> than other <jats:italic>HLA-DQA1<\/jats:italic> alleles. In silico 3D structural models were also applied to investigate the validity of the energetic stability of pMHCs. Taken together, our findings indicate that <jats:italic>HLA-DQA1*05:03<\/jats:italic> possesses a distinct property to play a pathogenic role in the development of NMOSD.<\/jats:p>","DOI":"10.1038\/s41598-021-04074-1","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T11:03:34Z","timestamp":1641553414000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["High cell surface expression and peptide binding affinity of HLA-DQA1*05:03, a susceptible allele of neuromyelitis optica spectrum disorders (NMOSD)"],"prefix":"10.1038","volume":"12","author":[{"given":"Shohei","family":"Beppu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Wilamowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadahiro","family":"Suenaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Yasumizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kotaro","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruyuki","family":"Ishikura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Tada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Koda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Murata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoyuki","family":"Shiraishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuko","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keigo","family":"Kihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Sugimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Arase","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daron M.","family":"Standley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsusada","family":"Okuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Mochizuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"4074_CR1","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1136\/jnnp-2012-302310","volume":"84","author":"A Jacob","year":"2013","unstructured":"Jacob, A. et al. 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