T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides.
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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; Merwe, van der; Anton, P; Jones, E Yvonne; Fugger, Lars.
in: IMMUNITY, Jahrgang 30, Nr. 3, 3, 2009, S. 348-357.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides.
AU - Harkiolaki, Maria
AU - Holmes, Samantha L
AU - Svendsen, Pia
AU - Gregersen, Jon W
AU - Jensen, Lise T
AU - McMahon, Roisin
AU - Friese, Manuel A.
AU - van Boxel, Gijs
AU - Etzensperger, Ruth
AU - Tzartos, John S
AU - Kranc, Kamil
AU - Sainsbury, Sarah
AU - Harlos, Karl
AU - Mellins, Elizabeth D
AU - Palace, Jackie
AU - Esiri, Margaret M
AU - Merwe, van der
AU - Anton, P
AU - Jones, E Yvonne
AU - Fugger, Lars
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 30
SP - 348
EP - 357
JO - IMMUNITY
JF - IMMUNITY
SN - 1074-7613
IS - 3
M1 - 3
ER -
