T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides

Harkiolaki, Maria, Holmes, Samantha L., Svendsen, Pia, Gregersen, Jon W., Jensen, Lise T., McMahon, Roisin, Friese, Manuel A., Van Boxel, Gijs, Etzensperger, Ruth, Tzartos, John S., Kranc, Kamil, Sainsbury, Sarah, Harlos, Karl, Mellins, Elizabeth D., Palace, Jackie, Esiri, Margaret M., van der Merwe, P. Anton, Jones, E. Yvonne and Fugger, Lars (2009) T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. Immunity, 30 3: 348-357. doi:10.1016/j.immuni.2009.01.009


Author Harkiolaki, Maria
Holmes, Samantha L.
Svendsen, Pia
Gregersen, Jon W.
Jensen, Lise T.
McMahon, Roisin
Friese, Manuel A.
Van Boxel, Gijs
Etzensperger, Ruth
Tzartos, John S.
Kranc, Kamil
Sainsbury, Sarah
Harlos, Karl
Mellins, Elizabeth D.
Palace, Jackie
Esiri, Margaret M.
van der Merwe, P. Anton
Jones, E. Yvonne
Fugger, Lars
Title T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides
Journal name Immunity   Check publisher's open access policy
ISSN 1074-7613
1097-4180
Publication date 2009-03-20
Sub-type Article (original research)
DOI 10.1016/j.immuni.2009.01.009
Volume 30
Issue 3
Start page 348
End page 357
Total pages 10
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Abstract Environmental factors account for 75% of the risk of developing multiple sclerosis (MS). Numerous infections have been suspected as environmental disease triggers, but none of them has consistently been incriminated, and it is unclear how so many different infections may play a role. We show that a microbial peptide, common to several major classes of bacteria, can induce MS-like disease in humanized mice by crossreacting with a T cell receptor (TCR) that also recognizes a peptide from myelin basic protein, a candidate MS autoantigen. Structural analysis demonstrates this crossreactivity is due to structural mimicry of a binding hotspot shared by self and microbial antigens, rather than to degenerate TCR recognition. Biophysical studies reveal that the autoreactive TCR binding affinity is markedly lower for the microbial (mimicry) peptide than for the autoantigenic peptide. Thus, these data suggest a possible explanation for the difficulty in incriminating individual infections in the development of MS.
Keyword Cellimmuno
Humdisease
Mollimmuno
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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Created: Mon, 25 Jul 2011, 12:16:52 EST by Susan Allen on behalf of Institute for Molecular Bioscience