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2011-06-12Zeitschriftenartikel DOI: 10.1016/j.ejcb.2011.03.003
HLA class I-associated diseases with a suspected autoimmune etiology: HLA-B27 subtypes as a model system
dc.contributor.authorUchanska-Ziegler, Barbara
dc.contributor.authorLoll, Bernhard
dc.contributor.authorFabian, Heinz
dc.contributor.authorHee, Chee Seng
dc.contributor.authorSaenger, Wolfram
dc.contributor.authorZiegler, Andreas
dc.date.accessioned2018-05-07T15:49:30Z
dc.date.available2018-05-07T15:49:30Z
dc.date.created2012-09-06
dc.date.issued2011-06-12none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/re75YIxgsWLPI/PDF/26yVljVGnO2o2.pdf
dc.identifier.urihttp://edoc.rki.de/176904/1274
dc.description.abstractAlthough most autoimmune diseases are connected to major histocompatibility complex (MHC) class II alleles, a small number of these disorders exhibit a variable degree of association with selected MHC class I genes, like certain human HLA-A and HLA-B alleles. The basis for these associations, however, has so far remained elusive. An understanding might be obtained by comparing functional, biochemical, and biophysical properties of alleles that are minimally distinct from each other, but are nevertheless differentially associated to a given disease, like the HLA-B*27:05 and HLA-B*27:09 antigens, which differ only by a single amino acid residue (Asp116His) that is deeply buried within the binding groove. We have employed a number of approaches, including X-ray crystallography and isotope-edited infrared spectroscopy, to investigate biophysical characteristics of the two HLA-B27 subtypes complexed with up to ten different peptides. Our findings demonstrate that the binding of these peptides as well as the conformational flexibility of the subtypes is greatly influenced by interactions of the C-terminal peptide residue. In particular, a basic C-terminal peptide residue is favoured by the disease-associated subtype HLA-B*27:05, but not by HLA-B*27:09. This property appears also as the only common denominator of distinct HLA class I alleles, among them HLA-B*27:05, HLA-A*03:01 or HLA-A*11:01, that are associated with diseases suspected to have an autoimmune etiology. We postulate here that the products of these alleles, due to their unusual ability to bind with high affinity to a particular peptide set during positive T cell selection in the thymus, are involved in shaping an abnormal T cell repertoire which predisposes to the acquisition of autoimmune diseases.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut
dc.subjectAnkylosing Spondylitiseng
dc.subjectAutoimmunityeng
dc.subjectHLA-B27 subtypeseng
dc.subjectHeavy chain flexibilityeng
dc.subjectInfrared spectroscopyeng
dc.subjectMultiple Sclerosiseng
dc.subjectPeptide binding modeseng
dc.subjectMicropolymorphismseng
dc.subjectT cell selectioneng
dc.subjectX-ray crystallographyeng
dc.subject.ddc610 Medizin
dc.titleHLA class I-associated diseases with a suspected autoimmune etiology: HLA-B27 subtypes as a model system
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10026804
dc.identifier.doi10.1016/j.ejcb.2011.03.003
dc.identifier.doihttp://dx.doi.org/10.25646/1199
local.edoc.container-titleEuropean Journal of Cell Biology
local.edoc.container-textUchanska-Ziegler, B., Loll, B., Fabian, H., Hee, C.S., Saenger, W., Ziegler, A. HLA class I-associated diseases with a suspected autoimmune etiology: HLA-B27 subtypes as a model system (2012) European Journal of Cell Biology, 91 (4), pp. 274-286.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.sciencedirect.com/science/article/pii/S0171933511000574
local.edoc.container-publisher-nameElsevier
local.edoc.container-volume91
local.edoc.container-issue4
local.edoc.container-year2012

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