Cloning of the major histocompatibility complex class II promoter binding protein affected in a hereditary defect in class II gene regulation.

Abstract:

:The regulation of major histocompatibility complex class II gene expression is directly involved in the control of normal and abnormal immune responses. In humans, HLA-DR, -DQ, and -DP class II heterodimers are encoded by a family of alpha- and beta-chain genes clustered in the major histocompatibility complex. Their expression is developmentally controlled and normally restricted to certain cell types. This control is mediated by cis-acting sequences in class II promoters and by trans-acting regulatory factors. Several nuclear proteins bind to class II promoter sequences. In a form of hereditary immunodeficiency characterized by a defect in a trans-acting regulatory factor controlling class II gene transcription, we have observed that one of these nuclear factors (RF-X) does not bind to its target sequence (the class II X box). A cDNA encoding RF-X was isolated by screening a phage expression library with an X-box binding-site probe. The recombinant protein has the binding specificity of RF-X, including a characteristic gradient of affinity for the X boxes of HLA-DR, -DP, and -DQ promoters. RF-X mRNA is present in the regulatory mutants, indicating a defect in the synthesis of a functional form of the RF-X protein.

authors

Reith W,Barras E,Satola S,Kobr M,Reinhart D,Sanchez CH,Mach B

doi

10.1073/pnas.86.11.4200

subject

Has Abstract

pub_date

1989-06-01 00:00:00

pages

4200-4

issue

11

eissn

0027-8424

issn

1091-6490

journal_volume

86

pub_type

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