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1. University of Kansas Medical Center, Kansas, KS 2. University of Nairobi, Nairobi, Kenya 3. University of Illinois at Chicago, Chicago, IL The human leukocyte antigen-G(HLA-G), a protein highly expressed at the human maternal-fetal interface during pregnancy, is thought to be critical for the survival of the semi-allogenic fetus. Current evidence suggests that HLA-G programs immune cells at the maternal-fetal interface into immunosuppressive phenotypes, but definitive proof remains elusive since the vivo experiments in humans are not possible due to ethical concerns. In the search for an appropriate animal model, we have identified the olive baboon (Papio anubis) as a potential candidate. The primate expresses an HLA-G-like protein termed Paan-AG n the placenta. Preliminary data shows that Paan-AG gene shares many characteristics with HLA-G, including limited polymorphism, alternative splicing of the mRNA, and restricted tissue expression of the protein. Restricted tissue expression suggested that the two genes might share tissue-specific regulatory elements. We previously identified a number of two Paan-AG alleles, 5'UTAG-1(AG1) and 5'UTAG-2(AG2). The objective of the current study was to assess binding of the transcription factor NF-kB to Paan-AG promoter activity. Both alleles contained two kB elements, kB1 and kB2. Binding was assessed using electrophoretic mobility shift assays and functional activity using luciferase reporter assays. NF-kB bound both kB1 and kB2 elements in the AG1 allele. In contrast, only kB1 of the AG-2 allele bound to NF-kB; kB2 did not bind. The AG2 kB1. Mutagenesis studies showed that the difference in binding was due to two alleles also differed; AG2 consistently showed higher luciferase activity compared to AG1. Mutating the last two nucleotides in the 3' end of kB1 resulted in an increase of luciferase activity to levels comparable to that of AG2. Overall, these results suggests that variations in the proximal promoter may influence transcription rates of Paan-AG as reported recently for HLA-G, and provide further evidence of the potential usefulness of the baboon as a model for in vivo HLA-G studies. Supported by NIH grant HD39878 (JSH)