The second and third amino acids of Pam2 lipopeptides are key for the proliferation of cytotoxic T cells

Yohei Takeda, Masahiro Azuma, Ryoko Hatsugai, Yukari Fujimoto, Masahito Hashimoto, Koichi Fukase, Misako Matsumoto, Tsukasa Seya

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The TLR2 agonist, dipalmitoyl lipopeptide (Pam2LP), has been used as an immune adjuvant without much success. Pam2LP is recognised by TLR2/6 receptors in humans and in mice. This study examined the proliferative activity of cytotoxic T lymphocytes (CTL) using mouse Ag-presenting dendritic cells (DCs) and OT-I assay system, where a library of synthetic Pam2LP was utilised from the Staphylococcus aureus database. Ag-specific CTL expansion and IFN-γ levels largely depended on the Pam2LP peptide sequence. The first Aa is cysteine (Cys), which has an active SH residue to bridge fatty acids, and the second and third Aa are hydrophilic or non-polar. The sequence structurally adapted to the residual constitution of the reported TLR2/6 pocket. The inactive sequence contained proline or leucine/isoleucine after the first Cys. Notably, no direct activation of OT-I cells was detected without DCs by stimulation with the active Pam2LP having the Cys-Ser sequence. MyD88, but not TICAM-1 or IFN pathways, in DCs participates in DC maturation characterised by upregulation of CD40, CD80 and CD86. Hence, the active Pam2LPs appear suitable for dimeric TLR2/6 on DCs, resulting in induction of DC maturation.

Original languageEnglish
JournalInnate Immunity
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Lipopeptides
Dendritic Cells
T-Lymphocytes
Amino Acids
Cysteine
Cytotoxic T-Lymphocytes
Toll-Like Receptor 2
Isoleucine
Constitution and Bylaws
Proline
Leucine
Libraries
Staphylococcus aureus
Up-Regulation
Fatty Acids
Databases
Peptides

Keywords

  • CTL proliferation
  • MyD88-mediated dendritic cell priming
  • Pam2 lipopeptide
  • TLR2 agonist

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

Cite this

The second and third amino acids of Pam2 lipopeptides are key for the proliferation of cytotoxic T cells. / Takeda, Yohei; Azuma, Masahiro; Hatsugai, Ryoko; Fujimoto, Yukari; Hashimoto, Masahito; Fukase, Koichi; Matsumoto, Misako; Seya, Tsukasa.

In: Innate Immunity, 01.01.2018.

Research output: Contribution to journalArticle

Takeda, Yohei ; Azuma, Masahiro ; Hatsugai, Ryoko ; Fujimoto, Yukari ; Hashimoto, Masahito ; Fukase, Koichi ; Matsumoto, Misako ; Seya, Tsukasa. / The second and third amino acids of Pam2 lipopeptides are key for the proliferation of cytotoxic T cells. In: Innate Immunity. 2018.
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