Bare lymphocyte syndrome (BLS) is an autosomal recessive severe-combined immunodeficiency that can result from mutations in four different transcription factors that regulate the expression of major histocompatibility complex (MHC) class II genes. We have identified here the defective gene that is responsible for the phenotype of the putative fifth BLS complementation group. The mutation was found in the regulatory factor that binds X-box 5 (RFX5) and was mapped to one of the arginines in a DNA-binding surface of this protein. Its wild-type counterpart restored binding of the RFX complex to DNA, transcription of all MHC class II genes and the appearance of these determinants on the surface of BLS cells.
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We thank P. Zupanc-Ecimovic for secretarial assistance; E. Vanin for the RD114 retroviral system and advice; G. Tosi for D1.12 and B7.21 antibodies; and other members of our laboratory for helpful discussions. Supported by the Peter und Traudl Engelhorn Stiftung (M. G.) and a grant from Nora Eccles Treadwell Foundation.
The authors declare no competing financial interests.
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Nekrep, N., Jabrane-Ferrat, N., Wolf, H. et al. Mutation in a winged-helix DNA-binding motif causes atypical bare lymphocyte syndrome. Nat Immunol 3, 1075–1081 (2002). https://doi.org/10.1038/ni840
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