MHC class II gene regulation is important during the induction and maintenance of primary and secondary immune responses. The bare lymphocyte syndrome (BLS) results from improper regulation of these genes. Analysis of these cases of BLS has proved to be very helpful in understanding the regulation of these genes. During the previous grant period, the investigator's research has been responsible for a large part of our understanding of how the expression of these genes is regulated. This has included a detailed description of the complexes formed between various factors and DNA elements in the promoter. Part of this has included the identification of a new factor, p41, which can be co-isolated with RFX. It is proposed that the assembly, modification and action of the RFX complex is a focal event in the initiation of class II gene expression as well as a potential point of regulation. In addition to RFX, the activator protein, CIITA, is involved in interactions with the RFX complex, other factors, and the basal transcription machinery. This proposal has as its aims: 1) To determine the nature of one of the remaining BLS complementation groups. 2) To determine the structural and functional aspects of the RFX complex. 3) To determine the role of phosphorylation of RFX subunits in class II expression. 4) Characterize the mechanism of CIITA action. The experimental approaches are predominantly biochemical.
