Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a class I coding sequence linked to a novel transcribed repetitive element.
We describe here the isolation and sequencing of a previously uncharacterized HLA class I gene. This gene, HLA-5.4, is the third non-HLA-A,B,C gene characterized whose sequence shows it encodes an intact class I protein. RNase protection assays with a probe specific for this gene demonstrated its expression in B lymphoblastoid cell lines, in resting T cells, and skin cells, while no mRNA could be detected in the T cell line Molt 4. Consistent with a pattern of expression different from that of other class I genes, DNA sequence comparisons identified potential regulator motifs unique to HLA-5.4 and possibly essential for tissue-specific expression. Protein sequence analysis of human and murine class I antigens has identified 10 highly conserved residues believed to be involved in antigen binding. Five of these are altered in HLA-5.4, and of these, three are nonconservative. In addition, examination of the HLA-5.4 DNA sequence predicts that the cytoplasmic segment of this protein is shorter than that of the classical transplantation antigens. The 3' untranslated region of the HLA-5.4 gene contains one member of a previously undescribed multigene family consisting of at least 30 members. Northern analysis showed that several of these sequences were transcribed, and the most ubiquitous transcript, a 600-nucleotide polyadenylated mRNA, was found in all tissues and cells examined. This sequence is conserved in the mouse genome, where a similar number of copies were found, and one of these sequences was also transcribed, yielding a 600-nucleotide mRNA. The characterization of this unique HLA class I gene and the demonstration of its tissue-specific expression have prompted us to propose that HLA-5.4 be designated HLA-F.
Geraghty
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Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
Wei
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Orr
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Koller
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D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics; D005091:Exons; D005805:Genes, MHC Class I; D008040:Genetic Linkage; D006680:HLA Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics; D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D006680:HLA Antigens; C062341:HLA-F antigens; D015395:Histocompatibility Antigens Class I; D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger; D012313:RNA; D004247:DNA