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Characterization of human gene encoding SLA/LP autoantigen and its conserved homologs in mouse,fish,fly,and worm

World Journal of Gastroenterology 2006年第6期12卷 902-907页

作者： Chun-Xia Wang Andreas Teufel Uta Cheruti joachim groetzinger Peter R Galle Ansgar W Lohse Johannes Herkel I. Department of Medicine University Medical Centre Hamburg-Eppendorf Hamburg Germany Shandong University Shandong Provincial Hospital Jinan Shandong Province China I. Department ofMedicine Johannes Gutenberg University Mainz Germany Institute of Biochemistry Christian-Albretchts-University Kiel Germany

AIM： To approach the elusive function of the SLA/LP molecule, we have characterized genomic organization and conservation of the major antigenic and functional properties of the SLA/LP molecule in various species. METHODS： By means of computational biology, we have characterized the complete SLA/LP gene, mRNA and deduced protein sequences in man, mouse, zebrafish, fly, and worm. RESULTS： The human SLA/LP gene sequence of approximately 39 kb, which maps to chromosome 4p15.2, is organized in 11 exons, of which 10 or 11 are translated, depending on the splice variant. Homologous molecules were identified in several biological model organisms. The various homologous protein sequences showed a high degree of similarity or homology, notably at those residues that are of functional importance. The only domain of the human protein sequence that lacks significant homology with homologous sequences is the major antigenic epitope recognized by autoantibodies from autoimmune hepatitis （AIH） patients. CONCLUSION： The SLA/LP molecule and its functionally relevant residues have been highly conserved throughout the evoluti n, suggesting an indispensable function of the molecule. The finding that the only non-conserved domain is the dominant antigenic epitope of the human SLA/LP sequence, suggests that SLA/LP autoimmunity is autoantigen-driven rather than being driven by molecular mimicry.

关键词： Autoimmune hepatitis Autoantigen Genomics Bioinformatics

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