HLA—A Central Immunological Agency of Man

Amos, D. Bernard; Kostyu, Donna D.

doi:10.1007/978-1-4615-8288-5_2

Cited by 31 publications

(21 citation statements)

References 267 publications

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“…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.…”

mentioning

confidence: 99%

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

Moriuchi¹,

Moriuchi²,

Silver³

1985

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

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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...

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mentioning

confidence: 99%

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

Moriuchi¹,

Moriuchi²,

Silver³

1985

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

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“…Genetic studies have shown that in each species there are a number of distinct loci within the MHC which encode class I heavy chains. Extensive serological (1,17) and biochemical analyses (24) of transplantation antigens, including detailed amino acid sequence determinations (6,25,38), have revealed that the heavy chains are highly polymorphic in humans, mice, and miniature swine. More than 50 different alleles at each locus have been identified in mice (18).…”

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confidence: 99%

“…For spot hybridization of the DNA from SLA genomic clones, 1 Davis et al (11). Photographs were taken with a Philips 400 electron microscope at a magnification of 3,300x.…”

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confidence: 99%

Specific association of repetitive DNA sequences with major histocompatibility genes.

Singer¹,

Lifshitz²,

Abelson³

et al. 1983

Mol. Cell. Biol.

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The DNA sequence organization of a 17.8-kilobase segment of porcine DNA, containing a functional major histocompatibility (MHC) The major histocompatibility complex (MHC) in humans and other vertebrates encodes a series of highly polymorphic cell-surface glycoproteins involved in a variety of immunological phenomena (18,29). The transplantation antigens (class I) are of particular interest in that they are targets in, and restricting elements for, cytotoxic lymphocyte reactions (43) and are probably the major antigens involved in graft rejection. These antigens consist of two associated polypeptides, a heavy chain (45,000 daltons) and a light chain identified as b2-microglobulin. Genetic studies have shown that in each species there are a number of distinct loci within the MHC which encode class I heavy chains. Extensive serological (1,17) and biochemical analyses (24) of transplantation antigens, including detailed amino acid sequence determinations (6,25,38), have revealed that the heavy chains are highly polymorphic in humans, mice, and miniature swine. More than 50 different alleles at each locus have been identified in mice (18). Thus, the heavy chains of transplantation antigens represent one of the most polymorphic multigene families known in eucaryotes. The mechanisms generating this diversity are not known. In contrast, b2-microglobulin, which is not encoded in the MHC, is essentially invariant within a species.The genetic complexity, diversity, and biological importance of the MHC have provided the impetus for numerous studies contributing to the characterization of this complex in a variety of species. Recently, this analysis has been extended to an assessment of the DNA sequence organization of the MHC, and a variety of genes encoding MHC antigens from humans (20,26,32), mice (7,13,35), and miniature swine (30) have been isolated. It has been estimated that the number of sequences homologous to class I heavy-chain genes ranges from about 12 in swine (30) to approximately 40 in some strains of mice (35). To date, analysis of DNA sequences of MHC genes from both humans (20) and mice (35) reveals the common eucaryotic gene organization: separate exons encode the three external polypeptide domains and the transmembrane and cytoplasmic segments. Studies on the structure of the MHC class I genes have led to the proposal (13) that the extensive polymorphism observed in the MHC may in part be generated by gene conversions in addition to more well defined mechanisms, such as point mutations and recombination. However, it is apparent that analyses of structural genes alone will not totally elucidate the regulatory events leading to differential expression of MHC genes and the generation of polymorphism, nor will they reveal the evolutionary processes occurring within the MHC.Another approach is to examine the organization and structure of DNA sequences linked to MHC genes. In mice the intergenic distances range from less than 10 kilobases (kb) to greater 903 on May 9, 2018 by guest

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“…Protein products encoded by the major histocompatibility complex (MHC) genes are involved in critical aspects of the im mune response: intracellular recognition and cooperation, alloreactivity, and immunoreactivity to foreign antigens, including a wide range of human viruses [1,2], The MHC is composed of closely linked genes located on chromosome 6 in humans, which determines a number of cell surface antigens responsible for tissue histocompatibility and immune re sponsiveness [3,4]. MHC class I (HLA-A, -B, -C) transplantation antigens are polymor phic and are composed of an MHC-encoded heavy chain noncovalently associated with a non-MHC-encoded light chain, p2-micro-globulin [5].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Major Histocompatibility Complex Gene Products in Tissues Isolated from the Developing Human Nervous System

Kollas

Hartle²,

Wigdahl³

1990

Fetal Diagn Ther

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We have examined the expression of the major histocompatibility complex (MHC) class I and II gene products in the developing human fetal peripheral nervous system. As determined by RNA blot hybridization analysis, MHC class I RNA was readily detectable in extracts prepared from dorsal root ganglia (DRG) obtained from aborted human fetal material. However, utilizing similar methodology, it was not possible to detect MHC class II RNA. In conjunction with these studies, expression of MHC class I and II proteins in primary human fetal DRG tissue was examined by fluorescence-activated flow cytometry and protein immunoblotting. Consistent with the detection of MHC-specific RNA, the accumulation of MHC class I-specific protein was readily detectable in human fetal DRG neural cell populations with little, if any, accumulation of MHC class II-specific protein evident. These studies suggest that MHC gene products may be expressed early in the development of the human nervous system resulting in the generation of specific immunocompetent neural cell populations.

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HLA—A Central Immunological Agency of Man

Cited by 31 publications

References 267 publications

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

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

Specific association of repetitive DNA sequences with major histocompatibility genes.

Analysis of Major Histocompatibility Complex Gene Products in Tissues Isolated from the Developing Human Nervous System

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