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Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor.

Abstract：

:Autoimmune diseases are caused by self-reactive lymphocytes that have escaped deletion. Here we have determined the structure of the trimolecular complex for a T cell receptor (TCR) from a patient with multiple sclerosis that causes autoimmunity in transgenic mice. The structure showed a TCR topology notably different from that of antimicrobial TCRs. Rather than being centered on the peptide-major histocompatibility complex, this TCR contacted only the N-terminal peptide segment and made asymmetrical interactions with the major histocompatibility complex helices. The interaction was dominated by the hypervariable complementarity-determining region 3 loops, indicating that unconventional topologies are possible because of the unique complementarity-determining region 3 sequences created during rearrangement. This topology reduces the interaction surface with peptide and alters the geometry for CD4 association. We propose that unusual TCR-binding properties can permit autoreactive T cells to escape deletion.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Hahn M,Nicholson MJ,Pyrdol J,Wucherpfennig KW

doi

10.1038/ni1187

keywords:

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

490-6

issue

5

eissn

1529-2908

issn

1529-2916

pii

ni1187

journal_volume

6

pub_type

杂志文章

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