Characterization and regulation of α-interferon receptor expression in interferon-sensitive and -resistant human lymphoblastoid cells

G. E. Hannigan, D. R. Gewert, B. R.G. Williams

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Abstract

Interferon-sensitive (IFN-S) and IFN-resistant (IFN-R) Daudi lymphoblastoid cells were studied for IFN-α receptor expression and regulation by steady state and kinetic procedures, utilizing a homogeneous 125I-IFN-α2 probe. Heterogeneity in the binding of this probe to IFN-S cells was determined to result from negatively cooperative interactions between an initially homogeneous class of IFN receptor. No such heterogeneity was noted in the IFN-R cells, indicating an apparent difference in the interaction of IFN-α2 with these cells. The apparent dissociation constants (K(d)) for IFN-S cell receptors were calculated to be 1 x 10-10 M and 1 x 10-8 M, for the high and low affinity sites, respectively. The K(d) for sites on the IFN-R cells was estimated to be 4 x 10-9 M. IFN-R and IFN-S cells expressed 2.4 x 104 and 3.5 x 104 binding sites per cell, respectively, representing an increase of at least 6-fold over previous reports of IFN-S Daudi IFN receptor density. Both IFN-S and IFN-R cells were capable of down-regulating expression of the IFN-α receptor in response to low concentrations of IFN-(α2). Furthermore, both cell lines were shown to be capable of internalizing specifically bound 125I-IFN-(α2) to an equivalent degree. Accordingly, we propose that the relative insensitivity of the Daudi IFN-R phenotype involves the loss of a high affinity interaction between cellular receptors and IFN-(α2), in addition to the reduced level of expressed low affinity binding sites.

Original languageEnglish
Pages (from-to)9456-9460
Number of pages5
JournalThe Journal of Biological Chemistry
Volume259
Issue number15
Publication statusPublished - 1 Jan 1984
Externally publishedYes

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