The half-life of the T-cell receptor/peptide–major histocompatibility complex interaction can modulate T-cell activation in response to bacterial challenge

Authors

  • Leandro J. Carreño,

    1. Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile
    2. Millennium Nucleus on Immunology and Immunotherapy, Santiago, Chile
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  • Susan M. Bueno,

    1. Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile
    2. Millennium Nucleus on Immunology and Immunotherapy, Santiago, Chile
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  • Paulina Bull,

    1. Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile
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  • Stanley G. Nathenson,

    1. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
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  • Alexis M. Kalergis

    1. Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile
    2. Departamento de Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
    3. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
    4. Millennium Nucleus on Immunology and Immunotherapy, Santiago, Chile
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Dr A. M. Kalergis, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda #340, Santiago, Chile.
Email: akalergis@bio.puc.cl
Senior author: Dr A. M. Kalergis

Summary

T-cell activation results from engagement of the T-cell receptor (TCR) by cognate peptide–major histocompatibility complex (pMHC) complexes on the surface of antigen-presenting cells (APC). Previous studies have provided evidence supporting the notion that the half-life of the TCR/pMHC interaction and the density of pMHC on the APC are two parameters that can influence T-cell activation. However, whether the half-life of the TCR/pMHC interaction can modulate T-cell activation in response to a pathogen challenge remains unknown. To approach this question, we generated strains of bacteria expressing variants of the ovalbumin (OVA) antigen, carrying point mutations in the SIINFEKL sequence. When bound to H-2Kb, this peptide is the cognate ligand for the OT-I TCR. Variants of the H-2Kb/SIINFEKL bind to the OT-I TCR with distinct half-lives. Here we show that dendritic cells (DCs) infected with bacteria expressing OVA variants were incapable of activating OT-I T cells when the half-life of the TCR/H-2Kb/OVA interaction was excessively short. Consistent with these data, T-cell activation was only observed in mice infected with bacteria expressing OVA variants that bound to OT-I with a half-life above a certain threshold. Considered together, our data suggest that the half-life of TCR/pMHC interaction can significantly modulate T-cell activation in vivo, as well as influence recognition of antigens expressed by bacteria. These observations underscore the importance of the TCR/pMHC half-life on the clearance of pathogens.

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