The complete nucleotide sequence of the I-Eα<sup>d</sup>immune response gene

Hyldig‐Nielsen, J. J.; Schenning, L.; Hammerling, Ulf; Widmark, E; Heldin, E; Lind, Peter; Servenius, B; Lund, Torben; Flavell, Richard A.; Lee, J S; Trowsdale, John; Schreier, Peter; Zablitzky, F; Larhammar, Dan; Peterson, Per A.; Rask, Lars

doi:10.1093/nar/11.15.5055

Cited by 88 publications

(31 citation statements)

References 45 publications

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“…Two segments of conserved nucleotides have previously been identified (25) in the 5' flanking regions of the human DRa gene (35) and the murine Ea (36,37) and Ef3 genes (25 (Fig. 4) shows that DRf84+ alone differs at the last The presence of tissue-specific transcriptional enhancer elements in the region preceding the putative promoter elements of a murine E,8 gene, the structural homologue of DR3, has recently been described (38).…”

mentioning

confidence: 85%

Characterization of an HLA DR beta pseudogene.

Larhammar¹,

Servenius²,

Rask³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

130

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The class II molecules of the human major histocompatibility complex include the DR, DC, and SB antigens, each composed of an a and a 13 polypeptide chain. We have isolated a DR13 gene in overlapping cosmid clones made from genomic DNA of a Dw4/DR4 homozygous individual. This gene consists of six exons and spans >20 kilobases. Upon sequencing, it was found to possess several deleterious mutations, each capable of rendering the gene nonfunctional: (i) four splice junctions deviate from the G-T/A-G rule; (ii) two premature termination codons are present in the first domain exon; (iii) a 2-base-pair insertion causes a translational frame shift in the second domain exon. In addition, several amino acid residues that are conserved in all known expressed (3 chains have been replaced in the amino acid sequence predicted from the pseudogene. Analysis of the pattern of nucleotide substitutions in the second domain exon suggests that most amino acid replacements occurred after the gene was inactivated. The inactivation may have been caused by insertion of a Kpn I repeat 5' to the promoter region, thereby interfering with transcription of the gene through removal of transcriptional enhancer elements. The DR(3 pseudogene seems to be present also in other DR4 individuals.The class II antigens of the major histocompatibility tomplex are expressed on some cell types involved in the immune response, such as B lymphocytes and macrophages (1). They participate in the presentation of foreign antigens in cellular interactions (2). In man, associations between class II antigen alleles and a large number of diseases have been described (3).The human major histocompatibility complex contains the genes of at least three types of class II antigens-i.e., DR, DC, and SB (4, 5). All three are cell-surface glycoprotein heterodimers, consisting of an a chain of -z35,000 Da noncovalently associated with a 13 chain of --28,000 Da (6). A characteristic property of the class II antigens is their extensive genetic polymorphism. The variability of the DR antigens is provided exclusively by the 13 chains (7) whose polymorphism resides primarily in the amino-terminal domains (8, 9).Cloning of cDNA (10) and protein sequencing (11,12) have shown that in some cell lines, DR13-like genes of at least two distinct loci are expressed. Hybridizations to genomic DNA with DR1B probes reveal even further complexity, inasmuch as individuals of different DR specificities seem to display distinct numbers of DR13 genes, some having at least three DRP-like genes (J. Bohme, personal communication).Class II antigen DNA probes are now being used in hybridizations to genomic DNA in search for more specific correlations of various diseases with class II loci and alleles, detected as restriction fragment length polymorphisms (13, 14). However, the hybridization patterns obtained often reveal a more complex genetic organization than expected from phenotypic observations (15). Molecular characterization of the many class II genes should help simplify interpretation...

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mentioning

confidence: 85%

Characterization of an HLA DR beta pseudogene.

Larhammar¹,

Servenius²,

Rask³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

130

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“…The E/k gene was derived from a construct consisting of the leader exon from the Ed gene and the remainder of the molecule from the Ek gene (unpublished data). As the leader peptide is excised prior to cell surface expression (leaving three apparently silent amino acid substitutions in the Ek NH2-terminal region), and the E. and E. subunits are almost identical (15,16), the expressed Ed/k and EkEd molecules are referred to here as E and I-Ed, respectively.…”

Section: Methodsmentioning

confidence: 99%

Ia-transfected L-cell fibroblasts present a lysozyme peptide but not the native protein to lysozyme-specific T cells.

Shastri¹,

Malissen²,

Hood³

1985

Proc. Natl. Acad. Sci. U.S.A.

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“…The sequences in this region for DCa, DXa, DC/3, and DXf3 are presented in Fig. 6 and compared to published sequences for I-AP (29), I-Ef3 (28), SB13(26), a DRp pseudogene (25), DRa (30), and I-Ea (31). The compilation of these sequences indicates, first of all, that the conserved sequences at -69 to -78 and -98 to -110 are also present in all four genes in the DC-DX clusters.…”

Section: Gag Gag Tac Ggg Cgc Ttc Gac Agc Gac Gtt Ggg Gag Ttc Cag Gcg mentioning

confidence: 99%