Cellular uptake followed by class I MHC presentation of some exogenous peptides contributes to T cell stimulatory capacity

Susan E. Brophy, Lindsay L. Jones, Phillip D. Holler, David M Kranz

Research output: Contribution to journalArticle

Abstract

The T cell stimulatory activity of peptides is known to be associated with the cell surface stability and lifetime of the peptide-MHC (pepMHC) complex. In this report, soluble high-affinity T cell receptors (TCRs) that are specific for pepMHC complexes recognized by the mouse CD8+ clone 2C were used to monitor the cell surface lifetimes of synthetic agonist peptides. In the 2C system, Ld-binding peptide p2Ca (LSPFPFDL) has up to 10,000-fold lower activity than peptide QL9 (QLSPFPFDL) even though the 2C TCR binds to p2Ca-Ld and QL9-Ld complexes with similar affinities. Unexpectedly, p2Ca-Ld complexes were found to have a longer cell surface lifetime than QL9-Ld complexes. However, the strong agonist activity of QL9 correlated with its ability to participate in efficient intracellular delivery followed by cell surface expression of the peptide, resulting in high and persistent surface levels of QL9-Ld. The ability of target cells to take up and present QL9 was observed with TAP-deficient cells and TAP-positive cells, including dendritic cells. The process was brefeldin A-sensitive, indicating a requirement for transport of the pepMHC through the ER and/or golgi. Thus, strong T cell stimulatory activity of some pepMHC complexes can be accomplished not only through long cell surface lifetimes of the ligand, but through a mechanism that leads to delayed presentation of the exogenous antigen after intracellular uptake.

Original languageEnglish (US)
Pages (from-to)2184-2194
Number of pages11
JournalMolecular Immunology
Volume44
Issue number9
DOIs
StatePublished - Mar 1 2007

Fingerprint

T-Lymphocytes
Peptides
T-Cell Antigen Receptor
Brefeldin A
Antigen Presentation
Dendritic Cells
Clone Cells
Ligands
p2Ca peptide

Keywords

  • Antigen presentation/processing
  • MHC
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Cite this

Cellular uptake followed by class I MHC presentation of some exogenous peptides contributes to T cell stimulatory capacity. / Brophy, Susan E.; Jones, Lindsay L.; Holler, Phillip D.; Kranz, David M.

In: Molecular Immunology, Vol. 44, No. 9, 01.03.2007, p. 2184-2194.

Research output: Contribution to journalArticle

Brophy, Susan E. ; Jones, Lindsay L. ; Holler, Phillip D. ; Kranz, David M. / Cellular uptake followed by class I MHC presentation of some exogenous peptides contributes to T cell stimulatory capacity. In: Molecular Immunology. 2007 ; Vol. 44, No. 9. pp. 2184-2194.
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