Differential role for CD277 as a co-regulator of the immune signal in T and NK cells

Authors

  • Nassima Messal,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
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  • Emilie Mamessier,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
    Current affiliation:
    1. Centre d'Immunologie Marseille-Luminy (CIML), Parc Scientifique de Luminy, 13288 Marseille, France
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    • These authors contributed equally to this work.

  • Aude Sylvain,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
    Current affiliation:
    1. Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Clayton, Victoria 3800, Australia
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    • These authors contributed equally to this work.

  • Javier Celis-Gutierrez,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
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  • Marie-Laure Thibult,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
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  • Bruno Chetaille,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
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  • Guylène Firaguay,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
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  • Sonia Pastor,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
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  • Yves Guillaume,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
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  • Qian Wang,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
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  • Ivan Hirsch,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
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  • Jacques A. Nunès,

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
    • Centre de Recherche en Cancérologie de Marseille, 27 Bd Leï Roure, BP 30059, 13273 Marseille, France Fax: +33-491-26-03-64
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  • Daniel Olive

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France
    2. Institut Paoli-Calmettes, F-13009, Mar seille, France
    3. Aix-Marseille Univ, F-13284, Marseille, France
    • Centre de Recherche en Cancérologie de Marseille, 27 Bd Leï Roure, BP 30059, 13273 Marseille, France Fax: +33-491-26-03-64
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Abstract

The human butyrophilin (BTN) 3 or CD277 molecules belong to the B7 family members and are expressed in various immune cells such as T and NK cells. Here, we show that CD277 triggering considerably enhances TCR-induced cytokine production and cell proliferation, even when another co-stimulatory molecule, CD28, is engaged. These CD277-induced additive functional effects are in accordance with the detection of early T-cell activation events such as TCR-induced cell signaling being increased upon CD277 engagement. However, we found that CD277 triggering is not involved in CD16- or NKp46-induced NK cell activation. BTN3/CD277 comprises three structurally related members, BTN3A1, BTN3A2 and BTN3A3. CD277 antibodies recognize all isoforms and we describe a differential expression of BTN3 isoforms between T and NK cells that could explain differential CD277 functions between T and NK cells. Our results show that, while T cells express all BTN3/CD277 transcripts, NK cells express mostly BTN3A2, which lacks the B30.2 intracellular domain. Furthermore, NKp30-induced cytokine production is decreased by the specific engagement of BTN3A2, but not by BTN3A1 triggering. Thus, we provide new insights into the CD277 co-stimulatory pathway that may differentially participate in the regulation of various cell-mediated immune responses.

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