Cloning ofthemajorhistocompatibili ty
1989
Theregulation ofmajorhistocompatibility complex class IIgeneexpression isdirectly involved inthe control ofnormal andabnormal immuneresponses. Inhu- mans,HLA-DR,-DQ,and-DPclass IIheterodimers are encoded byafamily ofa-andfl-chain genes clustered inthe majorhistocompatibility complex. Their expression isdevel- opmentally controlled andnormally restricted tocertain cell types. Thiscontrol ismediated bycis-acting sequences inclass IIpromoters andbytrans-acting regulatory factors. Several nuclear proteins bindtoclass IIpromoter sequences. Inaform ofhereditary immunodeficiency characterized byadefect ina trans-acting regulatory factor controlling class IIgenetran- scription, wehaveobserved that oneofthese nuclear factors (RF-X) does notbindtoits target sequence (the class HXbox). A cDNAencoding RF-Xwasisolated byscreening aphage expression library withanX-boxbinding-site probe. The recombinant protein hasthebinding specificity ofRF-X, including acharacteristic gradient ofaffinity fortheXboxes of HLA-DR, -DP,and-DQpromoters. RF-XmRNAispresent in theregulatory mutants, indicating adefect inthesynthesis of afunctional formoftheRF-Xprotein.
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