Agonist/endogenous peptide-MHC heterodimers drive T cell activation and sensitivity.
Published
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Krogsgaard, M; Li, Q-J; Sumen, C; Huppa, JB; Huse, M; Davis, MM
Published Date
- March 10, 2005
Published In
Volume / Issue
- 434 / 7030
Start / End Page
- 238 - 243
PubMed ID
- 15724150
Pubmed Central ID
- 15724150
Electronic International Standard Serial Number (EISSN)
- 1476-4687
Digital Object Identifier (DOI)
- 10.1038/nature03391
Language
- eng
Conference Location
- England