OBJECTIVE: The HLA-B27 allele is strongly associated with the group of inflammatory diseases known as the spondylarthritides (SpA). The aim of this study was to perform a large-scale, direct biochemical analysis of the HLA-B*2705 peptidome in order to identify candidates for mimicry between HLA-B27 peptides derived from cartilage proteins and arthritogenic bacterial sequences and to refine the consensus binding motif of this important allele. METHODS: The peptides were recovered by recombinant expression of soluble HLA-B27 molecules secreted from cultured chondrocytic cells or HeLa cells. Analysis was based on capillary chromatography and tandem mass spectrometry in combination with stable isotope labeling with amino acids in cell culture or chemical labeling with iTRAQ to enhance the validity of the data. RESULTS: Over 1,268 B27 peptides were identified, with 569 of them at high certainty, thus enabling better refinement of the B27 motif. This enabled the prediction of both short peptides and long peptides whose middle residues likely bulge out of the binding groove. Moreover, we identified a number of human B27 peptide sequences derived from human cartilage proteins, some of which are similar to common bacterial sequences. CONCLUSION: The peptides we identified may provide the missing link between bacterial infections and the resulting SpA.
OBJECTIVE: The HLA-B27 allele is strongly associated with the group of inflammatory diseases known as the spondylarthritides (SpA). The aim of this study was to perform a large-scale, direct biochemical analysis of the HLA-B*2705 peptidome in order to identify candidates for mimicry between HLA-B27 peptides derived from cartilage proteins and arthritogenic bacterial sequences and to refine the consensus binding motif of this important allele. METHODS: The peptides were recovered by recombinant expression of soluble HLA-B27 molecules secreted from cultured chondrocytic cells or HeLa cells. Analysis was based on capillary chromatography and tandem mass spectrometry in combination with stable isotope labeling with amino acids in cell culture or chemical labeling with iTRAQ to enhance the validity of the data. RESULTS: Over 1,268 B27 peptides were identified, with 569 of them at high certainty, thus enabling better refinement of the B27 motif. This enabled the prediction of both short peptides and long peptides whose middle residues likely bulge out of the binding groove. Moreover, we identified a number of humanB27 peptide sequences derived from humancartilage proteins, some of which are similar to common bacterial sequences. CONCLUSION: The peptides we identified may provide the missing link between bacterial infections and the resulting SpA.
Authors: Julie Boucau; Julien Madouasse; Georgio Kourjian; Christopher S Carlin; Daniel Wambua; Matthew J Berberich; Sylvie Le Gall Journal: J Immunol Date: 2019-04-01 Impact factor: 5.422
Authors: Bernhard Loll; Christine Rückert; Chee Seng Hee; Wolfram Saenger; Barbara Uchanska-Ziegler; Andreas Ziegler Journal: Protein Sci Date: 2010-12-23 Impact factor: 6.725
Authors: Miguel Marcilla; Adán Alpízar; Manuel Lombardía; Antonio Ramos-Fernandez; Manuel Ramos; Juan Pablo Albar Journal: Mol Cell Proteomics Date: 2013-12-23 Impact factor: 5.911
Authors: Chopie Hassan; Eric Chabrol; Lorenz Jahn; Michel G D Kester; Arnoud H de Ru; Jan W Drijfhout; Jamie Rossjohn; J H Frederik Falkenburg; Mirjam H M Heemskerk; Stephanie Gras; Peter A van Veelen Journal: J Biol Chem Date: 2014-12-12 Impact factor: 5.157
Authors: Eilon Barnea; Dganit Melamed Kadosh; Yael Haimovich; Nimman Satumtira; Martha L Dorris; Mylinh T Nguyen; Robert E Hammer; Tri M Tran; Robert A Colbert; Joel D Taurog; Arie Admon Journal: Mol Cell Proteomics Date: 2017-02-10 Impact factor: 5.911
Authors: Marijana Rucevic; Georgio Kourjian; Julie Boucau; Renata Blatnik; Wilfredo Garcia Bertran; Matthew J Berberich; Bruce D Walker; Angelika B Riemer; Sylvie Le Gall Journal: J Virol Date: 2016-09-12 Impact factor: 5.103