Abstract
The baboon major histocompatibility complex (MHC) class Ib gene, Paan-AG, is structurally similar to the human MHC class Ia gene, HLA-A, but exhibits characteristics similar to those of the class Ib gene HLA-G. These include limited polymorphism, alternative splicing of a single message, and restricted tissue distribution, with high expression in the placenta. In order to determine whether regulatory elements controlling expression of Paan-AG resemble those of HLA-A or HLA-G, we cloned the 5′ and 3′ untranslated regions of Paan-AG. Unexpectedly, sequence comparisons showed that potential regulatory elements in Paan-AG strikingly resembled those in HLA-A and differed in major respects from those in HLA-G. Unlike HLA-G, Paan-AG contained an intact interferon-γ stimulated response element (ISRE) in the promoter. Studies using luciferase reporter assays showed that the Paan-AG ISRE was functional. The basal activity of the Paan-AG ISRE and its response to interferon-γ was similar to that of class Ia MHC genes. Further, we identified an ISRE in the 3′ untranslated region of Paan-AG that is known to be functional in HLA-A2 but is deleted in HLA-G. These experiments predict that functional studies may demonstrate differences in regulation of expression of Paan-AG and HLA-G genes, which could restrict the use of the baboon as a primate model for studying HLA-G expression and function.
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Acknowledgements
This study was funded in part by CONRAD/CICCR grant no. 640510 and NIH grant POI HD39878 (Project III) to J.S.H. Support was provided by the Kansas Reproductive Sciences Center and the Kansas Biomedical Research Infrastructure Network grant (RR16475, NCRR, J.S.H, Principal Investigator).
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The nucleotide sequence data reported in this paper are available in the DDBJ/EMBL/GenBank databases under accession numbers AY434095, AY434096, AY434097 and AY434103.
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Langat, D.K., Morales, P.J., Fazleabas, A.T. et al. Potential regulatory sequences in the untranslated regions of the baboon MHC class Ib gene, Paan-AG, more closely resemble those in the human MHC class Ia genes than those in the class Ib gene, HLA-G. Immunogenetics 56, 657–666 (2004). https://doi.org/10.1007/s00251-004-0727-5
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DOI: https://doi.org/10.1007/s00251-004-0727-5