{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:53:00Z","timestamp":1783597980403,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T00:00:00Z","timestamp":1479168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HLA"],"published-print":{"date-parts":[[2017,1]]},"abstract":"Abstract<\/jats:title>Toxic shock syndrome toxin\u20101 (TSST<\/jats:styled-content>\u20101) is a potent superantigen produced by Staphylococcus aureus<\/jats:italic>. In addition to menstrual and nonmenstrual toxic shock syndromes, TSST<\/jats:styled-content>\u20101 is also implicated in the immunopathogenesis of pneumonia, infective endocarditis, neonatal exanthematous disease, and atopic dermatitis among others. Superantigens first bind to major histocompatibility complex (MHC<\/jats:styled-content>) class II<\/jats:styled-content> molecules and then activate a large proportion of T cells by cross\u2010linking their T cell receptor. As binding to MHC<\/jats:styled-content> class II<\/jats:styled-content> molecules is a critical step in the robust activation of the immune system by TSST<\/jats:styled-content>\u20101 and other superantigens, polymorphic variations between different HLA\u2010DR<\/jats:styled-content> alleles could potentially influence the magnitude of immune activation and immunopathology caused by TSST<\/jats:styled-content>\u20101. As TSST<\/jats:styled-content>\u20101 is highly toxic to humans and given that multiple variations of alleles of HLA\u2010DR<\/jats:styled-content> and HLA\u2010DQ<\/jats:styled-content> are expressed in each individual, it is difficult to determine how HLA\u2010DR<\/jats:styled-content> polymorphisms quantitatively and qualitatively impact immune activation caused by TSST<\/jats:styled-content>\u20101 in humans. However, such investigations can be conducted on transgenic mice lacking all endogenous MHC<\/jats:styled-content> class II<\/jats:styled-content> molecules and expressing specific HLA<\/jats:styled-content> class II<\/jats:styled-content> alleles. Therefore, transgenic mice expressing different HLA\u2010DRB1<\/jats:styled-content> alleles (HLA\u2010DRB1<\/jats:styled-content>*15:01<\/jats:italic>, HLA\u2010DRB1<\/jats:styled-content>*15:02<\/jats:italic>, HLA\u2010DRB1<\/jats:styled-content>*03:01<\/jats:italic>, HLA\u2010DRB1<\/jats:styled-content>*04:01<\/jats:italic>), and sharing HLA\u2010A1<\/jats:styled-content>*01:01<\/jats:italic> chain, were systemically challenged with purified TSST<\/jats:styled-content>\u20101 and multiple immune parameters were assessed. Among the HLA\u2010DR<\/jats:styled-content> alleles, mice expressing HLA\u2010DRB1<\/jats:styled-content>*15:01<\/jats:italic> allele elicited a significantly higher serum cytokine\/chemokine response; greater splenic T cell expansion and most severe organ pathology. Our study highlights the potential utility of human leukocyte antigen (HLA<\/jats:styled-content>) transgenic mice in understanding the impact of HLA<\/jats:styled-content> polymorphisms on the outcomes of diseases caused by TSST<\/jats:styled-content>\u20101 and other superantigens.<\/jats:p>","DOI":"10.1111\/tan.12930","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T19:25:59Z","timestamp":1479324359000},"page":"20-28","source":"Crossref","is-referenced-by-count":20,"title":["HLA\u2010DR<\/scp> polymorphisms influence in vivo<\/i> responses to staphylococcal toxic shock syndrome toxin\u20101 in a transgenic mouse model"],"prefix":"10.1111","volume":"89","author":[{"given":"A.","family":"Krogman","sequence":"first","affiliation":[{"name":"Department of Immunology Mayo Clinic College of Medicine Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Tilahun","sequence":"additional","affiliation":[{"name":"Department of Immunology Mayo Clinic College of Medicine Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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