High-frequency and adaptive-like dynamics of human CD1 self-reactive T cells

Authors

  • Claudia de Lalla,

    1. Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, DIBIT, San Raffaele Scientific Institute, Milano, Italy
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    • These authors contributed equally to this work.

  • Marco Lepore,

    1. Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, DIBIT, San Raffaele Scientific Institute, Milano, Italy
    Current affiliation:
    1. Experimental Immunology, Department of Biomedicine, University Hospital Basel, Switzerland
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    • These authors contributed equally to this work.

  • Francesco M. Piccolo,

    1. Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, DIBIT, San Raffaele Scientific Institute, Milano, Italy
    Current affiliation:
    1. Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London, UK
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  • Anna Rinaldi,

    1. Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, DIBIT, San Raffaele Scientific Institute, Milano, Italy
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  • Andrea Scelfo,

    1. Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, DIBIT, San Raffaele Scientific Institute, Milano, Italy
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  • Claudio Garavaglia,

    1. Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, DIBIT, San Raffaele Scientific Institute, Milano, Italy
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  • Lucia Mori,

    1. Experimental Immunology, Department of Biomedicine, University Hospital Basel, Switzerland
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  • Gennaro De Libero,

    1. Experimental Immunology, Department of Biomedicine, University Hospital Basel, Switzerland
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  • Paolo Dellabona,

    Corresponding author
    1. Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, DIBIT, San Raffaele Scientific Institute, Milano, Italy
    • Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, DIBIT, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milano, Italy Fax: +39-02-2643-4786
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  • Giulia Casorati

    Corresponding author
    1. Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, DIBIT, San Raffaele Scientific Institute, Milano, Italy
    • Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, DIBIT, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milano, Italy Fax: +39-02-2643-4786
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Abstract

CD1 molecules present lipid antigens to T cells. An intriguing subset of human T cells recognize CD1-expressing cells without deliberately added lipids. Frequency, subset distribution, clonal composition, naïve-to-memory dynamic transition of these CD1 self-reactive T cells remain largely unknown. By screening libraries of T-cell clones, generated from CD4+ or CD4CD8 double negative (DN) T cells sorted from the same donors, and by limiting dilution analysis, we find that the frequency of CD1 self-reactive T cells is unexpectedly high in both T-cell subsets, in the range of 1/10–1/300 circulating T cells. These T cells predominantly recognize CD1a and CD1c and express diverse TCRs. Frequency comparisons of T-cell clones from sorted naïve and memory compartments of umbilical cord and adult blood show that CD1 self-reactive T cells are naïve at birth and undergo an age-dependent increase in the memory compartment, suggesting a naïve/memory adaptive-like population dynamics. CD1 self-reactive clones exhibit mostly Th1 and Th0 functional activities, depending on the subset and on the CD1 isotype restriction. These findings unveil the unanticipated relevance of self-lipid T-cell response in humans and clarify the basic parameters of the lipid-specific T-cell physiology.

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