Molecular identification of human Ia antigens coded for by a gene locus closely linked toHLA-DR locus

Tanigaki, Nobuyuki; Tosi, Roberto; Pressman, David; Ferrara, Giovanni Battista

doi:10.1007/bf01561564

Cited by 69 publications

(27 citation statements)

References 21 publications

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“…One well known segregant series was defined during the Seventh and Eighth International Histocompatibility Workshops and includes HLA-DR1 through HLA-DRw10 (2,3). In addition, several other class II antigenic serological specificities have been described by different nomenclatures, such as MB, MT, DC, or BR (4)(5)(6)(7).…”

Section: Dr5mentioning

confidence: 99%

Molecular characterization of MT3 antigens by two-dimensional gel electrophoresis, NH2-terminal amino acid sequence analysis, and southern blot analysis.

Sorrentino¹,

Lillie²,

Strominger³

1985

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

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The monoclonal antibody 109d6, which In most recent years, the utilization of monoclonal antibodies directed to major histocompatibility complex (MHC) products and the molecular cloning of their genes have contributed enormously to the elucidation of the nature of the polymorphism and of the genetic organization of the HLA region. Multiple genes and pseudogenes coding for at least seven human light chains (8) and at least six heavy chains (9) have been described. Biochemical and serological evidence allowed these HLA genes to be grouped into three subregions named DR (DR), DC (DQ), and SB (DP). (The descriptions in parentheses are those indicated for the DR, DC, and SB subregions at the recent Ninth International Histocompatibility Workshop.) However, an important set of related questions remains to be answered-i.e., what is the exact number of expressed loci for each subregion and, in regard to the serological and cellular definitions of these molecules, what is the distribution of antigenic determinants among the expressed products of these loci and the extent of the polymorphism within different subsets of class II molecules?Indeed, a structural polymorphism among DR4 homozygous cell lines of both DR4 and DC4 light chains has been recently reported (10). It is interesting that the degree of variation is higher for DR than for DC molecules, suggesting that products of different loci may display different degrees of polymorphism. No more than five alleles, for instance, have been described for the products of the SB loci (11). Supertypic specificities, as defined by alloantisera, represent the sharing of a determinant that, at the population level, segregates with two or more DR alleles. It is interesting to examine the molecules carrying these allospecificities to establish if the homology is limited to a single determinant or involves a broader part of the molecule. This paper focuses on the biochemical characterization of the MT3 supertypic specificity by two-dimensional gel electrophoresis, protein sequence, and Southern blot analysis and shows that a MT3-like determinant is carried by an identical subset of DR molecules shared between DR4 and DR7 homozygous cell lines. The NH2-terminal amino acid analysis of MT3 and DR4 ,B chains shows that the two molecules differ in their primary structure. Southern blot analysis of genomic DNA from cell lines homozygous for DR] through DR7 suggests that the sharing of MT3 between DR4 and DR7 haplotypes is part of a broader homology between the two haplotypes. MATERIALS AND METHODSOne-and Two-Dimensional Gel Electrophoresis. The human lymphoblastoid B-cell lines were obtained from the Genetics Laboratory, Oxford University (Oxford, England), and were typed as part of the Seventh International Histocompatibility Workshop (Oxford, England) (12). The monoclonal antibodies L243, L227, LKT111, and 109d6 have been described (13)(14)(15)(16). Cells were labeled with the appropriate radioactive amino acid (1-2 mCi of 35S or 5 mCi of 3H, New England Nuclear; 1 Ci = 37 GBq...

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Section: Dr5mentioning

confidence: 99%

Molecular characterization of MT3 antigens by two-dimensional gel electrophoresis, NH2-terminal amino acid sequence analysis, and southern blot analysis.

Sorrentino¹,

Lillie²,

Strominger³

1985

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

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“…Molecules that express these alloantigenic determinants are known as class II or human Ia molecules. The HLA-DR antigenic system, which is highly polymorphic, can be distinguished from the others on the basis of immunodepletion (1)(2)(3), capping studies (4), and two-dimensional (2-D) gel analysis (5). Similarly, SB defines a distinct alloantigenic system on the basis of detection by primed lymphocytes and a genetic location distinct from and centromeric to HLA-DR (6).…”

mentioning

confidence: 99%

Further characterization of HLA-DS molecules: implications for studies assessing the role of human Ia molecules in cell interactions and disease susceptibility.

Goyert¹,

Silver²

1983

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

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HLA-DS molecules, the human homologs of murine I-A molecules, were analyzed and compared to DR molecules by two-dimensional gel analysis. These analyses allowed us to define six forms of DS molecules, suggesting that DS molecules were as polymorphic as DR molecules. The supertypic specificities, MT1 and MB3 were localized to DS molecules, whereas MT3 appeared to represent a crossreactive determinant present on products of two different loci encoding Ia-like molecules in man, a DS4 molecule and a DR7-like molecule. These studies also revealed that MT1 molecules isolated from DRI and DR2 cell lines were different, as were MB3 molecules isolated from DR4 and DR5 cell lines. Extensive crossreactions between DR and DS molecules were observed by using several monoclonal antibodies. This sharing of epitopes between products of different loci for human Ia molecules has important functional implications.

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“…Therefore, the reactivity of the above monoclonals is not restricted to the Ia supertypic specificities described up to now [3,4]. Moreover, comparison of peptic digests of NG1 and NG2 Ia subsets analyzed by two-dimensional peptide mapping has indicated that the two subsets display significant structural differences [7].…”

Section: Discussionmentioning

confidence: 99%

“…Recent molecular pool consists of distinct subsets of molecules which can be detected by specific antisera. Thus, it has been possible to identify Ia subsets clearly distinct from the classical HLA-DR molecules apparently expressed only in individuals with a given HLA-DR phenotype [3,4]. In addition, other Ia subsets have been identified which are present in all individuals, irrespective of their HLA-DR phenotype; they have been named Ia isotypes [5,61.…”

Section: Introductionmentioning

confidence: 99%

Demonstration at the single‐cell level of the existence of distinct clusters of epitopes in two predefined human Ia molecular subsets

Accolla¹,

Sékaly²,

McDonald³

et al. 1982

Eur J Immunol

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The expression at the cell surface level of two previously defined human Ia antigen subsets, NG1 and NG2, was studied. Two monoclonal hybridoma antibodies, D1-12 (anti-NG1) and D4-22 (anti-NG2), labeled with distinct fluorochromes, were used as probes. The results indicate that NG1 and NG2 molecules are simultaneously expressed on the same cell, and moreover, that they are identifiable as spatially separate structures. In addition, when a series of 6 other anti-Ia monoclonal antibodies previously described were analyzed in a checkerboard test of binding inhibition at the cell surface level, they were found to closely mimic the reactivity pattern of either D1-12 or D4-22 antibody, suggesting that NG1 and NG2 Ia subsets express independent clusters of highly immunogenic epitopes.

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Molecular identification of human Ia antigens coded for by a gene locus closely linked toHLA-DR locus

Cited by 69 publications

References 21 publications

Molecular characterization of MT3 antigens by two-dimensional gel electrophoresis, NH2-terminal amino acid sequence analysis, and southern blot analysis.

Molecular characterization of MT3 antigens by two-dimensional gel electrophoresis, NH2-terminal amino acid sequence analysis, and southern blot analysis.

Further characterization of HLA-DS molecules: implications for studies assessing the role of human Ia molecules in cell interactions and disease susceptibility.

Demonstration at the single‐cell level of the existence of distinct clusters of epitopes in two predefined human Ia molecular subsets

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