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Biological function and distribution of human interleukin‐12 receptor β chain
Author(s) -
Wu ChangYou,
Warrier Rajeev R.,
Carvajal Daisy M.,
Chua Anne O.,
Minetti Lisa J.,
Chizzonite Richard,
Mongini Patricia K. A.,
Stern Alvin S.,
Gubler Ueli,
Presky David H.,
Gately Maurice K.
Publication year - 1996
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830260212
Subject(s) - biology , function (biology) , distribution (mathematics) , interleukin 1 receptor, type ii , microbiology and biotechnology , computational biology , interleukin , immunology , interleukin 5 , cytokine , mathematical analysis , mathematics
Abstract We previously described the cloning of a cDNA encoding an interleukin‐12 receptor (IL‐12R) subunit, designated β, 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‐12Rβ chain, when used in combination, strongly inhibited IL‐12‐induced proliferation of activated T cells, IL‐12‐induced secretion of interferon‐γ 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‐12Rβ 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‐12Rβ 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‐12Rβ 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‐12Rβ 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‐12Rβ, but did not bind measurable amounts of IL‐12. These results indicate that expression of IL‐12Rβ 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‐12Rβ.