Biological function and distribution of human interleukin-12 receptor β chain
| Autor: | Maurice K. Gately, Lisa J. Minetti, Anne O. Chua, Alvin S. Stern, Richard Anthony Chizzonite, Daisy Carvajal, Rajeev R. Warrier, Ueli Gubler, David H. Presky, Chang-You Wu, Patricia K. A. Mongini |
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| Rok vydání: | 1996 |
| Předmět: |
T cell
Molecular Sequence Data Palatine Tonsil Immunology Cell Separation Biology Lymphocyte Activation Binding Competitive Cell Line Interleukin 21 medicine Humans Immunology and Allergy IL-2 receptor B cell B-Lymphocytes Binding Sites Base Sequence ZAP70 Receptors Interleukin-12 Antibodies Monoclonal Receptors Interleukin Natural killer T cell Interleukin-12 Molecular biology medicine.anatomical_structure Interleukin-12 receptor Leukocytes Mononuclear Interleukin 12 |
| Zdroj: | European Journal of Immunology. 26:345-350 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.1830260212 |
| Popis: | We previously described the cloning of a cDNA encoding an interleukin-12 receptor (IL-12R) subunit, designated beta, that bound IL-12 with low affinity when expressed in COS cells. We now report that a pair of monoclonal antibodies (mAb), 2B10 and 2.4E6, directed against different epitopes on the IL-12R beta chain, when used in combination, strongly inhibited IL-12-induced proliferation of activated T cells, IL-12-induced secretion of interferon-gamma by resting peripheral blood mononuclear cells (PBMC), and IL-12-mediated lymphokine-activated killer cell activation. The mAb had no effect on lymphoblast proliferation induced by IL-2, -4, or -7. Thus, the IL-12R beta chain appears to be an essential component of the functional IL-12R on both T and natural killer (NK) cells. We previously observed that high affinity IL-12R were expressed on activated T and NK cells, but not B cells. Studies using flow cytometry and reverse transcription-polymerase chain reaction analysis showed that IL-12R beta chain was expressed on several human T, NK, and (surprisingly) B cell lines, but not on non-lymphohematopoietic cell lines. The Kit225/K6 (T cell) and SKW6.4 (B cell) lines were found to express the greatest amounts of IL-12R beta chain (800-2500 sites/cell); however, Kit225/K6 but not SKW6.4 cells bound IL-12. Similar to SKW6.4 B cells, activated tonsillar B lymphocytes expressed IL-12R beta chain but, consistent with previous results, did not display detectable IL-12 binding. Likewise, up to 72% of resting PBMC from normal volunteer donors expressed IL-12R beta, but did not bind measurable amounts of IL-12. These results indicate that expression of IL-12R beta is essential, but not sufficient, for expression of functional IL-12R. We speculate that expression of functional, high-affinity IL-12R may require the presence of a second subunit that is more restricted in its expression than IL-12R beta. |
| Databáze: | OpenAIRE |
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