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Default polyfunctional T helper 1 response to ample signal 1 alone.

Luca Danelli1, Georgina Cornish1, Julia Merkenschlager1,2

  • 1Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.

Cellular & Molecular Immunology
|April 22, 2020
PubMed
Summary

Amplifying T-cell receptor (TCR) signal 1 alone during vaccination selectively expands high-affinity CD4+ T cells. This approach induces protective Th1 responses against infection and tumors.

Keywords:
CD4 T cell primingT helper differentiationpeptide-MHC II complex

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Area of Science:

  • Immunology
  • Vaccinology
  • T cell biology

Background:

  • CD4+ T cells require T-cell receptor (TCR) and costimulatory signals for activation.
  • Current vaccination strategies have limited ability to direct T helper (Th) cell subset expansion.

Purpose of the Study:

  • To investigate the immunogenicity of amplified signal 1 in the absence of costimulation.
  • To determine the Th subset bias induced by exclusive TCR signal amplification.
  • To assess the protective capacity of T cells primed via amplified signal 1.

Main Methods:

  • Development of cell-based vaccines with optimized peptide:MHC II (pMHC II) complexes.
  • Selective amplification of TCR signal 1 without classic costimulation.
  • Assessment of T cell expansion, polyfunctionality, and protective immunity against retroviral infection and tumor challenge.

Main Results:

  • Amplified signal 1 alone was immunogenic, expanding high-affinity TCR clonotypes.
  • Exclusive TCR signal amplification induced exclusively polyfunctional Th1 effector and memory cells.
  • Vaccination with amplified signal 1 conferred protection against retroviral infection and tumor challenge.
  • Expanded tumor-reactive CD4+ T cells in tumor-bearing hosts.

Conclusions:

  • Ample TCR signal 1 drives a default Th1 response.
  • Selective TCR signal amplification offers a novel strategy for priming protective Th1 responses via vaccination.