Three common alleles of KIR2DL4 (CD158d) encode constitutively expressed, inducible and secreted receptors in NK cells

• Published in: European Journal of Immunology 2007-01, Vol.37 (1), p.199-211
• Main Authors: Goodridge, Jodie P., Lathbury, Louise J., Steiner, Noriko K., Shulse, Christine N., Pullikotil, Philomena, Seidah, Nabil G., Hurley, Carolyn K., Christiansen, Frank T., Witt, Campbell S.
• Format: Article
• Language: English
• Subjects: Alleles; Antibodies, Monoclonal - metabolism; Antigen-Antibody Reactions - genetics; Cell Line; Cell Membrane - genetics; Cell Membrane - immunology; Cell Membrane - metabolism; Cells, Cultured; Humans; Killer Cells, Natural - immunology; Killer Cells, Natural - secretion; KIR2DL4; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; NK cells; Polymorphism, Genetic; Receptors; Receptors, Immunologic - biosynthesis; Receptors, Immunologic - genetics; Receptors, Immunologic - immunology; Receptors, Immunologic - metabolism; Receptors, KIR; Receptors, KIR2DL4; RNA Splicing - genetics; RNA Splicing - immunology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Solubility
• ISSN: 0014-2980; 1521-4141; 1365-2567
• DOI: 10.1002/eji.200636316

Genetic polymorphism of KIR2DL4 results in alleles with either 9 or 10 consecutive adenines in exon 6, which encodes the transmembrane domain. "10A" alleles encode a membrane‐expressed receptor that is constitutively expressed on resting CD56bright NK cells and on CD56dim cells after culture. However, in some individuals with the 10A allele, KIR2DL4 cannot be detected on their resting CD56bright NK cells. "9A" alleles have been predicted to encode a secreted receptor due to the splicing out of the transmembrane region. In this publication, we show that those individuals with a 10A allele who lack detectable KIR2DL4 on CD56bright NK cells express a KIR2DL4 receptor in which the D0‐domain is excised. This Δ‐D0 receptor cannot be detected by the available anti‐KIR2DL4 monoclonal antibodies. In such individuals, KIR2DL4 becomes detectable on cultured NK cells due to up‐regulation of the full‐length KIR2DL4 transcript. In all individuals with 10A alleles, KIR2DL4 ceases to be expressed at the cell surface 16 days after activation, despite the maintenance of maximal levels of KIR2DL4 mRNA transcription, suggesting the existence of a negative regulator of cell surface expression. Finally, we show that the 9A allele can produce a secreted KIR2DL4 receptor.