Arthritis-related B cell epitopes in collagen II are conformation-dependent and sterically privileged in accessible sites of cartilage collagen fibrils.

The Journal of Biological Chemistry
S SchulteHarald Burkhardt

Abstract

In collagen-induced arthritis, a murine autoimmune model for rheumatoid arthritis, immunization with native but not heat-denatured cartilage-specific collagen type II (CII) induces a B cell response that largely contributes to arthritogenicity. Previously, we have shown that monoclonal antibodies established from arthritis prone DBA/1 mice require the triple-helical conformation of their epitopes for antigen recognition. Here, we present a novel approach to characterize arthritis-related conformational epitopes by preparing a panel of 130 chimeric collagen X/CII molecules. The insertion of a series of CII cassettes into the triple-helical recombinant collagen X allowed for the first time the identification of five triple-helical immunodominant domains of 5-11 amino acid length, to which 75% of 36 monoclonal antibodies bound. A consensus motif, "R G hydrophobic," was found in all immunodominant epitopes. The antibodies were encoded by a certain combination of V-genes in germline configuration, indicating a role of the consensus motif in V-gene selection. The immunodominant domains are spread over the entire monomeric CII molecule with no apparent order; however, a highly organized arrangement became apparent when the CII molecul...Continue Reading

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Citations

Jun 10, 2009·Cell and Tissue Research·Kutty Selva Nandakumar
Jun 4, 2008·Modern Rheumatology·Merrill J RowleyRikard Holmdahl
Feb 12, 2004·Journal of Immunological Methods·Robyn E GrayMerrill J Rowley
Feb 11, 2009·The Journal of Experimental Medicine·Hüseyin UysalRikard Holmdahl
Jul 31, 2004·Immunology and Cell Biology·S Fatemah AmirahmadiMerrill J Rowley
Jul 4, 2006·Arthritis Research & Therapy·Stefan CarlsenRikard Holmdahl
Jan 27, 2007·Arthritis Research & Therapy·Kutty Selva Nandakumar, Rikard Holmdahl
Nov 30, 2000·Arthritis Research·U Müller-Ladner, K Nishioka
Nov 30, 2000·Arthritis Research·R Holmdahl
Apr 16, 2005·European Journal of Immunology·Harald BurkhardtRikard Holmdahl
Oct 1, 2008·European Journal of Immunology·Ulrika BöiersHarald Burkhardt
Dec 1, 2011·Arthritis and Rheumatism·Doreen DobritzschRikard Holmdahl
Dec 15, 2012·Arthritis and Rheumatism·Allyson M CroxfordMerrill J Rowley
Jul 28, 2010·Arthritis and Rheumatism·Allyson M CroxfordMerrill J Rowley
Mar 3, 2010·Immunological Reviews·Hüseyin UysalRikard Holmdahl
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Oct 2, 2007·Arthritis and Rheumatism·Kutty Selva NandakumarRikard Holmdahl
Feb 27, 2015·Current Protocols in Mouse Biology·Akhilesh Kumar Shakya, Kutty Selva Nandakumar
Mar 1, 2007·Expert Review of Clinical Immunology·Juha RisteliLeila Risteli
Jul 5, 2002·The Journal of Biological Chemistry·Marko SankalaTimo Pikkarainen
Apr 23, 2002·Scandinavian Journal of Immunology·M HolmdahlR Holmdahl

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