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

• Published in: European journal of immunology Vol. 41; no. 12; pp. 3443 - 3454
• Main Authors: Messal, Nassima, Mamessier, Emilie, Sylvain, Aude, Celis‐Gutierrez, Javier, Thibult, Marie‐Laure, Chetaille, Bruno, Firaguay, Guylène, Pastor, Sonia, Guillaume, Yves, Wang, Qian, Hirsch, Ivan, Nunès, Jacques A., Olive, Daniel
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.12.2011; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Subjects: Animals; Antigens, CD - immunology; Butyrophilin; Butyrophilins; Cancer; CD28 Antigens - immunology; CD4-Positive T-Lymphocytes - immunology; Cell activation; Cell Line, Transformed; Cell Proliferation; Cercopithecus aethiops; COS Cells; Co‐stimulatory molecules; Cytokines - immunology; Cytokines - metabolism; Humans; Immune system; Immunology; Immunotherapy; Interferon-gamma - immunology; Killer Cells, Natural - immunology; Life Sciences; Lymphocyte Activation - immunology; Lymphocyte receptors; Natural Cytotoxicity Triggering Receptor 3 - immunology; Protein Isoforms; Receptors, Antigen, T-Cell - immunology; T cell receptors; T cells; Up-Regulation
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201141404

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.