Sequences related to HLA-DR alpha chain on human chromosome 6: restriction enzyme polymorphism detected with DC alpha chain probes.

Three families of human Ia molecules, DP, DQ, and DR, have previously been defined. A cDNA clone, pDSH-9.1, encoding the a chain of a DQ molecule derived from an HLA-DRw9 homozygous cell line has been isolated and sequenced. Comparison of the nucleotide and predicted protein sequence to those of other DQ a subunits reveals that DQ a subunits derived from DR4, -7, and -9 cells are very similar to each other but quite different from a DQ a subunit derived from a DRw6 cell line. These studies suggest that certain Ia haplotypes have a common evolutionary history. Furthermore, in the context of current serologic and biochemical knowledge, they suggest that the gene encoding the DQ a subunit is in strong linkage disequilibrium with the DR locus.The Ia region of the major histocompatibility complex (MHC) consists of a series of closely linked loci encoding cell surface molecules that regulate the immune response. These Ia molecules may be divided into three groups, DP (formerly known as SB) (1), DQ (formerly known as DS) (2), and DR (3), that are structurally distinct. Ia molecules consist of two subunits, a and ,3, with molecular weights of approximately 28,000 and 33,000. Within each group, DP, DQ, and DR, multiple a-and /8-chain gene loci have been described; at present seven P3 chain (two DP, two DQ, and three DR) and five a chain (two DP, two DQ, and one DR) gene loci have been identified (4-9). Although their precise genetic order is not yet known, the DP locus is known to be centromeric to both DQ and DR, which in turn are centromeric to the class I loci, HLA-A, -B, and -C (10). Recombinational analysis indicates that both DP and the class I loci are approximately 1 centimorgan from the DQ and DR loci (10,11). No recombinational event between DQ and DR has yet been confirmed, suggesting a relatively low frequency of recombination. Biochemical studies (2,(12)(13)(14)(15)(16)(17)(18) and analysis of cDNA clones (19)(20)(21)(22)(23)(24)(25)(26) indicate that a majority of the Ia genes are expressed as products. Ia gene products belonging to the same group are highly related (greater than 95% protein homology) while those belonging to different groups are only approximately 60% related.The Ia system is highly polymorphic. At least 11 alleles at the DR locus (designated numerically-i.e., DR1-DR11) have been defined serologically (27). Similarly, at least 6 alleles at the DQ locus and 6 at the DP locus have been defined biochemically and by cellular assays, respectively (27,28 (29). Similarly, cells typing as DR1, -2, and -6 frequently display the MB1 antigenic determinant (30).Although the molecular basis for these antigenic determinants is not known, in some instances, the gene products expressing them have been identified. Thus, MB1, which is expressed on Drl, -2, and -6 cells, and MB3, which is expressed on DR4 and DR5 cells, are both present on different allelic forms of DQ molecules (28,31,32). In other instances, the molecular assignment has been more controversial; MT3 has been localized to DR-like mol...

Section: Dq9supporting

confidence: 74%

Nucleotide sequence of an HLA-DQ alpha chain derived from a DRw9 cell line: genetic and evolutionary implications.

Moriuchi¹,

Moriuchi²,

Silver³

1985

“…A partial nucleotide sequence (data not shown) allowed us to identify the SB achain gene on the basis of its identity with a published sequence of an SB a-chain cDNA (22). From both restriction fragment size and partial sequence, this a-chain gene is homologous to the gene described by Trowsdale et al (23).…”

Section: Discussionmentioning

confidence: 99%

Molecular organization of the HLA-SB region of the human major histocompatibility complex and evidence for two SB beta-chain genes.

Gorski¹,

Rollini²,

Long³

et al. 1984

The class II products of the major histocompatibility complex, also called Ia antigens, are composed of two polypeptide chains, the a and P chains, both encoded within the major histocompatibility complex. In man, the class II antigens can be divided into three biochemically distinct grodps called HLA-DR, HLA-DC, and HLA-SB. Our isolation of cDNA clones for the polymorphic fi chain of HLA-DR and HLA-DC has allowed us to study the organization of the class II genes. Here we identify the HLA-SB (-chain gene in recombinant clones from a cosmid library generated from a consanguineous homozygous B-cell line. The SB 3-chain gene is linked to the SB a-chain gene and the two genes are in opposite orientation. A second SB (&chain gene, corresponding to a new SB 3II locus, has also been identified and cloned. The SB 3chain genes show much less allelic restriction site polymorphism than the genes for the ( chains of HLA-DR or HLA-DC. MATERIALS AND METHODSConstruction of the Cosmid Library. Details of the cosmid library will be published elsewhere. In brief, DNA from the consanguineous homozygous cell line HHK was partially digested with Sau3A1 and fractionated on sucrose density gradients. DNA fractions of 35-40 kilobases (kb) were collected and ligated with arms of cosmid pOPF (12), which had been treated with phosphatase. The ligation mix was packaged in vitro (13) and introduced into Escherichia coli ED8767. The packaged cosmids were spread, replicated (14), and screened by colony filter hybridization (15). A DNA fragment from a DR p-chain genomic clone (unpublished data) labeled by nick-translation was used for these hybridizations. Colonies that were positive after three rounds of screening were grown and cosmid DNA was prepared.Identification of a Possible SB f3 cDNA Clone. The cloning of class II p-chain cDNA clones from a DR4,w6 cell line has been described (9 (Fig. 1) 3934The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

“…Study of the DC subregion was initiated by isolation of DCa (8) and DCB cDNA clones (9), followed by isolation and sequencing of the corresponding genomic clones (10)(11)(12). When the isolated cDNA clones were used as probes, Southern blots of DNA from a homozygous cell line indicated the presence of two closely related a gene bands, named DCa and DXa (4,(13)(14)(15) and two (or more) / gene bands (12,(16)(17)(18)(19). A genomic clone for DXa was also isolated and sequenced (10).…”

mentioning

confidence: 99%

Gene organization of DC and DX subregions of the human major histocompatibility complex.

Okada¹,

Boss²,

Prentice³

et al. 1985

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