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 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

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature03391

Language

  • eng