T Cell-Mediated Autoimmune Disease Due to Low-Affinity Crossreactivity to Common Microbial Peptides

被引：142

作者：

Harkiolaki, Maria ^{[1
]}

Holmes, Samantha L. ^{[1
,2
]}

Svendsen, Pia ^{[3
]}

Gregersen, Jon W. ^{[3
]}

Jensen, Lise T. ^{[3
]}

McMahon, Roisin ^{[1
,2
]}

Friese, Manuel A. ^{[2
,5
]}

van Boxel, Gijs ^{[1
]}

Etzensperger, Ruth ^{[2
,5
]}

Tzartos, John S. ^{[5
]}

Kranc, Kamil ^{[2
]}

Sainsbury, Sarah ^{[1
]}

Harlos, Karl ^{[1
]}

Mellins, Elizabeth D. ^{[4
]}

Palace, Jackie ^{[5
]}

Esiri, Margaret M. ^{[6
]}

van der Merwe, P. Anton ^{[7
]}

Jones, E. Yvonne ^{[1
]}

Fugger, Lars ^{[2
,3
,5
]}

机构：

[1] Univ Oxford, Div Struct Biol, Oxford OX3 7BN, England

[2] Univ Oxford, MRC Human Immunol Unit, Weatherall Inst Mol Med, John Radcliffe Hosp, Oxford OX3 9DS, England

[3] Aarhus Univ Hosp, Inst Clin, DK-8200 Aarhus N, Denmark

[4] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA

[5] Univ Oxford, Dept Clin Neurol, John Radcliffe Hosp, Oxford OX3 9DS, England

[6] Univ Oxford, Dept Neuropathol, John Radcliffe Hosp, Oxford OX3 9DS, England

[7] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

来源：

IMMUNITY | 2009年 / 30卷 / 03期

基金：

英国医学研究理事会;

关键词：

MYELIN BASIC-PROTEIN; CLASS-II MOLECULE; MULTIPLE-SCLEROSIS; STRUCTURAL BASIS; CRYSTAL-STRUCTURE; SELF-PEPTIDE; TCR BINDING; HLA-DR; RECEPTOR; MHC;

D O I：

10.1016/j.immuni.2009.01.009

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 pepticle. Thus, these data suggest a possible explanation for the difficulty in incriminating individual infections in the development of MS.

引用

页码：348 / 357

页数：10

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