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

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Item Type:	Article
Title:	Agonist/endogenous peptide-MHC heterodimers drive T cell activation and sensitivity
Creators Name:	Krogsgaard, M., Li, Q.J., Sumen, C., Huppa, J.B., Huse, M. and Davis, M.M.
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.
Keywords:	Amino Acid Sequence, Antigen Presentation, Antigen-Presenting Cells, CD4-Positive T-Lymphocytes, CHO Cells, Calcium Signaling, Cricetinae, Dimerization, HLA Antigens, Interleukin-2, Lipid Bilayers, Lymphocyte Activation, Molecular Sequence Data, Peptides, alpha-beta T-Cell Antigen Receptors, Sensitivity and Specificity, Animals, Mice
Source:	Nature
ISSN:	0028-0836
Publisher:	Nature Publishing Group
Volume:	434
Number:	7030
Page Range:	238-43
Date:	10 March 2005
Official Publication:	https://doi.org/10.1038/nature03391
PubMed:	View item in PubMed

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