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  • MHC  (2)
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  • 1
    ISSN: 1432-1211
    Keywords: Key words DRB6 ; MHC ; Primates ; Readingthrough mechanism ; Selenocysteine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The defective major histocompatibility complex (MHC) DRB6 gene is transcribed into mRNA in human [peripheral blood lymphocytes, transfected and Epstein-Barr virus (EBV)] and chimpanzee EBV cell lines. MHC-DRB6 presents several anomalies, which include stop codons in exon 2, lack of the usual polyadenilation signal of other MHC-DRB genes, and a promoter region and exon 1 taken from a locally inserted retrovirus. The complete cDNA sequences from human DRB6*0201 and three common chimpanzee alleles (Patr-DRB6*0108, Patr-DRB6*0109, Patr-DRB6*0111) have been obtained; two exon 1-exon 2 cDNA sequences from bonobos (Papa-DRB6*0101 and Papa-DRB6*0102) are also shown. In contrast to chimpanzee DRB6 transcripts, the human ones: (1) present an exon 1-exon 2 splicing site that includes the transcription of the first 141 nucleotides of intron 1, rendering a longer exon 1, and (2) show a duplication of exon 6, which would render a longer cytoplasmic tail in a putative DRB6 protein. These two characteristics are found in all the human sequences obtained, regardless of the cellular type tested, and they are not present in any of the chimpanzee alleles reported; consequently, they are human-specific. All the alleles reported here bear stop codons in the three possible reading frames; however, a certain level of expression of DRB6 has been observed by cytofluorometry. This could be due to the presence of a selenocysteine insertion sequence (SECIS) stem-loop structure located at the 3 untranslated region of the DRB6 mRNA, which directs selenocysteine incorporation at UGA codons. DRB6 transcription and translation would be the first gene model of a readingthrough stop codon mechanism in primate MHC. It is also feasible that the DRB6 gene might generate a population of short polypeptides, bound to plasmatic membranes, having non-antigen-presenting functions or which are presented by other MHC molecules as HLA-E presents HLA-G and -B leader sequence-derived peptides.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1211
    Keywords: Key words HLA ; MHC ; DRB6 ; LTR ; Retrovirus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  HLA-DRB6 is one of the human major histocompatibility complex (MHC) genes present in DR1, DR2, and DR10 haplotypes (approximately 26% of individuals). It shows several anomalies in human and non-human primates, including exon 2 stop codons (non-randomly grouped between codons 74 and 94) and a promoter region, and an exon 1 coming from an inserted retrovirus. It has been shown that not only chimpanzee but also human Mhc-DRB6 lack the usual 3’ untranslated (UT) polyadenylation signal, and in the present work it was found that the human DRB6 gene coming from an HLA-DR2 haplotype is effectively transcribed after transfection in mouse L cells, and that HLA-DRB6 molecules may be expressed on the cell surface. DRB6 transcription level is remarkably lower in human than in chimpanzee. Moreover, their exons 1 (both taken from the 3’LTR region of a mammary tumor retrovirus) are also different; this shows that these viral insertions may be an important mechanism for different evolutionary changes in orthologous genes of different species. The pathways by which DRB6 molecules may be expressed on the membrane are unclear but other examples of truncated protein expression have also been described, even within the human major histocompatibility complex (i. e., in HLA-G). Finally, the presence of mature HLA-DRB6 mRNA molecules supports the notion that splicing may take place even in the absence of a canonical 3’UT polyadenylation signal.
    Type of Medium: Electronic Resource
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