Agonist/endogenous peptide-MHC heterodimers drive T cell activation and sensitivity.

Abstract:

:Alphabeta T lymphocytes are able to detect even a single peptide-major histocompatibility complex (MHC) on the surface of an antigen-presenting cell. This is despite clear evidence, at least with CD4+ T cells, that monomeric ligands are not stimulatory. In an effort to understand how this remarkable sensitivity is achieved, we constructed soluble peptide-MHC heterodimers in which one peptide is an agonist and the other is one of the large number of endogenous peptide-MHCs displayed by presenting cells. We found that some specific combinations of these heterodimers can stimulate specific T cells in a CD4-dependent manner. This activation is severely impaired if the CD4-binding site on the agonist ligand is ablated, but the same mutation on an endogenous ligand has no effect. These data correlate well with analyses of lipid bilayers and cells presenting these ligands, and indicate that the basic unit of helper T cell activation is a heterodimer of agonist peptide- and endogenous peptide-MHC complexes, stabilized by CD4.

journal_name

Nature

journal_title

Nature

authors

Krogsgaard M,Li QJ,Sumen C,Huppa JB,Huse M,Davis MM

doi

10.1038/nature03391

keywords:

subject

Has Abstract

pub_date

2005-03-10 00:00:00

pages

238-43

issue

7030

eissn

0028-0836

issn

1476-4687

pii

nature03391

journal_volume

434

pub_type

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