Methods of identifying compounds useful for treating autoimmune diseases
AssigneePresident and Fellows of Harvard College
InventorsLaurie H. Glimcher, Hong Zhou, John Douhan, III
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Abstract
Disclosed are methods of identifying compounds which inhibit transcription activation by CIITA and thus inhibit MHC class II gene expression. Such compounds can affect the induction of an immune response. The methods employ, independently, the activation and interactions domains of CIITA. The methods also employ the activation and interaction domains of isotype-specific CIITA proteins, allowing for the identification of compounds which are isotype-specific inhibitors of transcription and which are useful for selectively affecting the immune system.
Claims25
A method of determining whether a compound inhibits the ability of a polypeptide to activate transcription, the polypeptide being characterized in that it comprises a CIITA transcription activation domain and lacks a functional CIITA interaction domain, wherein inhibition of transcription indicates that said compound is a potential autoimmune disease therapeutic.
A substantially pure DNA encoding a CIITA isotype-specific transcription activating polypeptide including amino acids 26-352 of SEQ ID NO:1, or a variant thereof that functions as an activation domain of CIITA but not as an interaction domain of CIITA.
A substantially pure DNA encoding a CIITA transcription activating polypeptide including amino acids 26-352 of SEQ ID NO:1, said polypeptide functioning as an activation domain but not as an interaction domain of CIITA.
A substantially pure polypeptide comprising a CIITA transcription activation domain and lacking a functional CIITA interaction domain.
A method of determining whether a compound inhibits the ability of a polypeptide to bind its target protein, said polypeptide being characterized in that it comprises a CIITA interaction domain and lacks a functional CIITA activation domain, wherein inhibition of binding indicates that said compound is a potential autoimmune disease therapeutic.
A substantially pure DNA encoding a CIITA polypeptide including amino acids 301-1139 of SEQ ID NO:1, or a variant thereof that functions as an interaction domain of CIITA, but not as an activation domain of CIITA.
A substantially pure polypeptide comprising a CIITA interaction domain and lacking a functional CIITA transcription activation domain.
A method of determining whether a compound inhibits the ability of a polypeptide to mediate transcription, said polypeptide being characterized in that it comprises a CIITA interaction domain fused to a transcription activation domain and lacks a functional CIITA transcription activation domain, wherein inhibition of transcription indicates that said compound is a potential autoimmune disease therapeutic.
Dependencies are inferred from the claim text.