Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Patent
1992-04-07
1997-05-27
Housel, James C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
530300, 530326, 530327, 530328, 530330, 514 2, 514 14, A61K 3900, A61K 3800, C07K 500, C07K 1600
Patent
active
056329881
DESCRIPTION:
BRIEF SUMMARY
Gamma interferon is a cytokine produced by activated helper T cells, one of the most characteristic activities of which is the upregulation of MHC class II gene expression in macrophages, mature B cells and T cells. The expression of class II antigens is a hallmark of antigen-presenting cells. Gamma interferon is also known to upregulate the expression of class II antigens in cells that are not primary antigen-presenting cells, such as epithelial cells, fibroblasts, astrocytes, endothelial cells and smooth muscle cells. The upregulation of class II antigens in these cell types is often correlated with the development of autoimmune disease.
Although the mechanism by which gamma interferon exerts its effects on cells is not understood, it is known that it binds to specific cellular receptors [Langer et al., Immunology Today 9:393 (1988)]. Aguet et al. [Cell 55:273 (1988)] have cloned and sequenced a gene for a gamma interferon receptor. The molecular weight of the encoded protein deduced from the sequence is consistent with the molecular weight of a gamma interferon receptor recently isolated from human placenta [Calderon et al., Proc. Natl. Acad. Sci. USA 85:4837 (1988)].
Because gamma interferon acts at specific cellular receptors and is implicated in autoimmune disease, agents which could inhibit the binding of such interferon to its cellular receptors might be useful therapeutically.
SUMMARY OF THE INVENTION
This invention provides novel polypeptides containing the amino acid subsequence Arg-Arg-Lys-Trp-Gln. More particularly, this invention provides novel polypeptides selected from the group consisting of:
The present invention further provides methods for inhibiting the binding of gamma interferon to cellular receptors, comprising contacting cells bearing receptors for gamma interferon with an effective amount of a polypeptide or protein selected from the group consisting of: residues; mixture of such residues; and and from 5 to about 30 amino acid residues, which polypeptide or protein has a Ki of about 25 .mu.M or less in inhibiting the specific binding of .sup.125 I-recombinant human gamma interferon to Daudi cells at 4.degree. C.
Because the polypeptides and proteins of the invention inhibit the binding of gamma interferon to its cellular receptors, they also inhibit the biological effects of such interferon such as antiviral effects and the induction of class II major histocompatibility antigens.
This invention thus also provides methods for inhibiting antiviral effects of gamma interferon, comprising contacting cells capable of responding to gamma interferon by producing an antiviral response with an effective amount of a polypeptide or protein selected from the group consisting of: residues; mixture of such residues; and and from 5 to about 30 amino acid residues.
This invention still further provides methods for inhibiting gamma interferon-induced expression of class II major histocompatibility antigens, comprising contacting cells capable of responding to gamma interferon by induction of expression of class II major histocompatibility antigens with an effective amount of a polypeptide or protein selected from the group consisting of: residues; mixture of such residues; and and from 5 to about 30 amino acid residues.
The polypeptides and methods of the present invention are useful for the in vitro study of the mechanism of gamma interferon binding to various cell types and for screening for agonists or other antagonists of such binding. They also have potential utility for the treatment of pathological conditions such as autoimmune disease, which are believed to be mediated by gamma interferon.
BRIEF DESCRIPTION OF THE FIGURES
This invention can be more readily understood by reference to the accompanying figures, in which:
FIG. 1 is a graphical representation of the inhibition by poly(D-lysine) (open squares) and poly(L-lysine) (closed squares) of the binding of 125I-recombinant human gamma interferon to Daudi cells. Percent specifically bound radioactivity is shown as a function of polyp
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Ingram Richard
Le Hung V.
Ramanathan Lata
Dulak Norman C.
Housel James C.
Lunn Paul G.
Minnifield N. M.
Schering Corporation
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