Murine I-Aβ Chain Polymorphism: Nucleotide Sequences of Three Allelic I-Aβ Genes

Choi, Edmund; McIntyre, Katherine; Germain, Ronald N.; Seidman, J. G.

doi:10.1126/science.6407114

Cited by 131 publications

(56 citation statements)

References 18 publications

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“…Restriction enzyme digestion and Southern blotting of clones in each class with the 32P-labeled 2918.4 probe upheld this assumption. Of 20 clones examined, only two different restriction patterns were observed, and clones of the A, class showed a pattern of restriction sites identical to the Ak gene (24). We isolated the longest cDNA insert from among the intensely hybridizing clones and subcloned it into pBR322 (pEB10).…”

Section: Methodsmentioning

confidence: 99%

Isolation and characterization of a cDNA clone for the murine I-E beta polypeptide chain.

Mengle-Gaw¹,

McDevitt²

1983

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

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The Ia antigens, encoded within the I region of the major histocompatibility complex, are a group of cell surface glycoproteins that are involved in the control of immune responsiveness. We isolated and determined the sequence of a 1,045-basepair cDNA clone for one of the murine immune response genes, EP. Comparison of the predicted amino acid sequence of the product of Eli with that of Ed shows that most of the amino acid differences are clustered in-short stretches of peptide sequence in the first external proteindomain. This clustering of allelic variation suggests that observed haplotype-specific immune responsiveness to certain antigens may be controlled, at least in part, by differences in configuration defined by these regions of allelic variability in the NH2-terminal domain of the E. chain.

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Section: Methodsmentioning

confidence: 99%

Isolation and characterization of a cDNA clone for the murine I-E beta polypeptide chain.

Mengle-Gaw¹,

McDevitt²

1983

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

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“…1. In addition, five 18-bp synthetic oligonucleotide primers homologous to conserved regions of the known AP and DQO sequences (8,(11)(12)(13)(14) were constructed and used to obtain sequence information on portions of the clones inaccessible from the EcoRI ends (Fig. 1, B-H productive (8, 9, 11-17).…”

mentioning

confidence: 99%

Sequence analysis and structure-function correlations of murine q, k, u, s, and f haplotype I-A beta cDNA clones.

Estess¹,

Begovich²,

Koo³

et al. 1986

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

100

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domain variability is clustered into three discrete regions, two of which divide the Ap chains into subgroups, suggesting an evolutionary history for the separation of alleles in inbred strains of mice. The amino acid sequences of these five chains are compared to each other and to previously published I-Ap chains. Correlations are made between the primary structural differences and the serologic and immune response characteristics mapping to the I-A subregion.The intimate relationship between I-region associated (Ia) antigens and immune responsiveness to a multitude of natural and synthetic antigens has been known for some time (1, 2).Recent studies using either anti-Ia antisera or monoclonal antibodies to block immune responses strongly suggest that Ia antigens are the products of immune response (Ir) genes (3-5), but how a limited number of Ia molecules differentially regulate responses to a myriad of antigens is yet to be resolved. It seems likely that their role in the presentation of antigen to imtnunocompetent cells is of fundamental importance and that primary structural alterations in the a and (3 chains of the class II heterodimer result in a failure to present antigen in a configuration appropriate for recognition. These alterations must also account for the multiple epitopes recognized by both anti-Ia antibodies and alloreactive T cells.In an effort to address the nature of primary structural differences among class II molecules and how these differences affect immune responses, we have undertaken the cloning and sequencing of cDNAs encoding I-Ap chains from several mouse haplotypes. This should facilitate the eventual assignment of particular serologic epitopes and restriction elements to specific amino acids in these chains. Such analysis is a first step in designing experiments in which immune responsiveness can be manipulated via structural alterations in Ia molecules and then, perhaps, understood. Clones hybridizing to the human DQp or the murine Al cDNA probes were tested for the presence of restriction enzyme sites consistent with AP but not Ed coding sequences (9). The longest such clones were subcloned into the EcoRI site ofpBR322 and from there into the EcoRI site of M13 mp8 for sequencing. Sequencing was performed by the dideoxysequencing method of Biggin et al. (10). All clones were sequenced using the M13 universal primer (UP) from the EcoRI ends, as shown in Fig. 1. In addition, five 18-bp synthetic oligonucleotide primers homologous to conserved regions of the known AP and DQO sequences (8,(11)(12)(13)(14) were constructed and used to obtain sequence information on portions of the clones inaccessible from the EcoRI ends (Fig. 1, B-H productive (8, 9, 11-17). MATERIALS AND METHODS

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“…This suggests that, in contrast to the weakly spliced human exon 4 (30), the mouse homolog is constitutively included in mature transcripts on the available haplotypes. Interestingly, examination of sequence alignments of the mouse (49,50) and the rat (51) introns showed a complete absence of tandem arranged G runs upstream of the predicted BPS. 4 This finding raises the hypothesis that the suprabranch G-rich ISEs identified in this study have been selected in humans to promote splicing of poorly recognized intron 3 and to maintain sufficient expression of natural DQB1 transcripts that encode membrane-bound molecules.…”

Section: Exon 4 Of the Mouse H2-ia␤ Is Constitutively Included In Mrnamentioning

confidence: 99%

Position-Dependent Repression and Promotion of DQB1 Intron 3 Splicing by GGGG Motifs

Královičová

Vořechovský

2006

The Journal of Immunology

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Alternative splicing of HLA-DQB1 exon 4 is allele-dependent and results in variable expression of soluble DQβ. We have recently shown that differential inclusion of this exon in mature transcripts is largely due to intron 3 variants in the branch point sequence (BPS) and polypyrimidine tract. To identify additional regulatory cis-elements that contribute to haplotype-specific splicing of DQB1, we systematically examined the effect of guanosine (G) repeats on intron 3 removal. We found that the GGG or GGGG repeats generally improved splicing of DQB1 intron 3, except for those that were adjacent to the 5′ splice site where they had the opposite effect. The most prominent splicing enhancement was conferred by GGGG motifs arranged in tandem upstream of the BPS. Replacement of a G-rich segment just 5′ of the BPS with a series of random sequences markedly repressed splicing, whereas substitutions of a segment further upstream that lacked the G-rich elements and had the same size did not result in comparable splicing inhibition. Systematic mutagenesis of both suprabranch guanosine quadruplets (G4) revealed a key role of central G residues in splicing enhancement, whereas cytosines in these positions had the most prominent repressive effects. Together, these results show a significant role of tandem G4NG4 structures in splicing of both complete and truncated DQB1 intron 3, support position dependency of G repeats in splicing promotion and inhibition, and identify positively and negatively acting sequences that contribute to the haplotype-specific DQB1 expression.

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Murine I-Aβ Chain Polymorphism: Nucleotide Sequences of Three Allelic I-Aβ Genes

Cited by 131 publications

References 18 publications

Isolation and characterization of a cDNA clone for the murine I-E beta polypeptide chain.

Isolation and characterization of a cDNA clone for the murine I-E beta polypeptide chain.

Sequence analysis and structure-function correlations of murine q, k, u, s, and f haplotype I-A beta cDNA clones.

Position-Dependent Repression and Promotion of DQB1 Intron 3 Splicing by GGGG Motifs

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