Split of HLA-DRw2 into subtypic specificities closely correlated to two HLA-D products

Richiardi, P.; Belvedere, Matteo; Borelli, I; Marchi, Mario; Curtoni, E. S.

doi:10.1007/bf01843988

Cited by 35 publications

(17 citation statements)

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“…Heterogeneity within individual DR haplotypes has been reported for DR2 (6,(39)(40)(41), DRw6 (42,43), DR7 (44)(45)(46)(47)(48), and DRw8 (49), as well as for DR4 (2,4,50). Each has been split on the basis of HLA-D reactivity.…”

Section: Discussionmentioning

confidence: 99%

Electrophoretic analysis of human HLA-DR antigens from HLA-DR4 homozygous cell lines: correlation between beta-chain diversity and HLA-D.

Nepom¹,

Nepom²,

Mickelson³

et al. 1983

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

119

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Two-dimensional gel electrophoresis of immunoprecipitated human HLA-DR antigens from cells expressing the HLA-DR4 haplotype shows distinct clustering of (3-chain patterns. Six unique electrophoretic variants were observed among 17 HLA-DR4 homozygous cell lines (HCL) analyzed. These patterns correlate precisely with the HLA-D phenotype of the HCL donor as determined by reactivity in mixed lymphocyte culture. All DR4 HCL that belong to one of the well-defined HLA-D antigen groups (Dw4, DwlO, LD "40", LD "DYI", LD "KT2", or LD "TAS") have identical DR (-chain . Comprehensive populations studies with DR4-associated HTC have led to the description of several distinct DR4-associated HLA-D antigens, including Dw4, DwlO, LD "40", LD "DYT", and LD "KT2" (4-8). There are several possible explanations for these apparent DR4 "splits." First, HLA-Dw4 and DR4 may be the products of different loci, each coding for distinct "D region"-associated antigens. A second possibility is that Dw4 and DR4 are products of a single gene, the primary product of which is recognized by DR4 alloantisera, but through post-translational modification sufficient phenotype variation occurs to cause the differences detected in MLC by T cells. In a third model, the haplotypes expressing Dw4, DwlO, LD 40, LD DYT, and LD KT2 may be encoded by different alleles but share a common crossreactive or "supertypic" determinant recognized by DR4 alloantisera.To answer such questions, we have begun a detailed analysis of the two-dimensional gel electrophoresis patterns of DR antigens expressed by B-lymphoblastoid cell lines (HCL) derived from HLA-DR4 homozygous donors. Since most of the polymorphism attributed to DR molecules has been correlated with structural heterogeneity of the DR (&chain (9-13), we have prepared cell lines from donors of HLA-D homozygous typing cells representing each of the distinct HLA-D antigens associated with DR4 and have studied the relationships among isolated DR4 ,3-chain polypeptides. Our results demonstrate a striking correlation between the functionally distinct HLA-D phenotypes of individual HCL and the two-dimensional gel patterns of the DR ,B chains isolated from these HCL.MATERIALS AND METHODS HCL. Seventeen B-lymphoblastoid cell lines homozygous for an HLA-DR4-associated D locus were used in this study (Table 1). The specificities Dw4, Dw10, LD 40, LD DYT, LD KT2, and DB3 have been defined by the Eighth Workshop (5), by Reinsmoen and Bach (4), and by Nose et al. (2). In addition, we have used HCL derived from a unique HTC, "TAS," described by Amar et al. (20), that is mutually reactive in MLC with cells from each of the other clusters and that may represent yet another apparent split of the DR4 haplotype.Established B-lymphoblastoid cell lines were available for some of the above HTC, otherwise new B-lymphoblastoid lines were prepared from cryopreserved HTC by cocultivation with Epstein-Barr virus (EBV) as described (21). Briefly, 1-2 X 106

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Section: Discussionmentioning

confidence: 99%

Electrophoretic analysis of human HLA-DR antigens from HLA-DR4 homozygous cell lines: correlation between beta-chain diversity and HLA-D.

Nepom¹,

Nepom²,

Mickelson³

et al. 1983

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

119

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“…Similarly, a new specificity, LD14 was ad-ded to the previously established list of DR2 associated HLA-D alleles, which include Dw2, DHO (Reinsmoen et al 1978, Sasazuki et al 1Y78), tb24 (Richardi et al 1978), and Dw9 as defined on our panel ). The DR phenotype of the LD14 HTC is virtually identical to that of Dw2 HTCs and of the Dw9 HTC, 8W20.5: they all type with the complete set of anti-DR2 and MT1 sera (Suciu-Foca et al 1979b.…”

Section: Discussionmentioning

confidence: 99%

“…they are all associated with D R 4 (Suciu-Foca et al 1978a, 1979a, 1979b, 1979c. Similarly, DR2 was found to be associated not only with Dw2, but also with three other distinct HLA-D alleles: Dw9 (as defined by HTC 8W205) (Suciu-Foca et al 1979b, 1979c, DHO (Reinsmoen et al 1978, Sasazuki et al 1978) and tb24 (Richardi et al 1978). Results obtained at the 8th International Histocompatibility Workshop (8W) confirmed the association of LD12 (or "DB3" in the Workshop analysis) and of DwlO with DR4, as well as the association between DHO (or "DB4") with DR2 (Dupont et al 1980).…”

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confidence: 94%

New HLA‐D Alleles Associated with DRI and DR2

et al. 1981

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The present study describes two new HLA‐D specificities: LD13, associated with DR1, and LD14 associated with DR2. LD13 is defined by an HTC who is the bc offspring of an a: A25, B18, DR7, Dw7/b: A33, B14, DR1, Dx father, and of a c: A24, B14, DR1, Dx/d: A26, B41, DR5, Dw5 mother. This HTC was included both as a responder and as a stimulator in our cross‐reference studies of 8W HTCs. While failing to cluster with any other 8W HTC, it typed 2 of 64 panel members carrying a “blank” HLA‐D, linked to DR1. To exclude the possibility that HTC‐LD13 might be a split of Dw1, the entire family was tested with the Family Set of 8W HTCs. No typing responses to any 8W Dw1 HTCs were observed. Furthermore, checkerboard experiments between HTC‐LD 13 and 8W Dw1 HTCs showed strong reciprocal stimulation. The LD13 specificity was only found in Ashkenazi Jews and may be in linkage disequilibrium with HLA‐B14. LD14 is defined by three, SD different, HTCs deriving from the same family of Sicilian descent. The family was included in the 8th Workshop and each HTC was shown to have inherited DR2, MT1 from both parents. When tested as stimulators, on our HLA‐D reference panel, these cells were clustered in a distinct group, LD14, associated with DR2. None of the 8W HTCs appeared to belong to this cluster. The antigen frequency of LD14 is 0.03.

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“…There is increasing evidence of the complexity of the HLA-D region as studied by cellular and serological techniques (Richiardi et al 1978, Reinsmoen & Bach 1982, Kasahara et al 1983) and more recently by molecular weight and surfacecharge variation of immunoprecipitated "Ialike" polypeptides (Groner et al 1983, Ka-Sahara et al 1983, Nepom et al 1983 [in press]). Haplotypes that appear to be homogeneous when studied with alloantisera specific for the HLA-DR locus often can be shown to be diverse when studied in functional assays of T cell recognition, such as the mixed lymphocyte culture reaction (MLR).…”

mentioning

confidence: 99%

“…In this manner, the HLA-DR4 haplotype has been shown to include at least five different HLA-D types and their corresponding gel patterns. Similarly, HTC have been used to define distinct HLA-D types within the DR2 and DRw8 haplotypes (Richiardi et al 1978, Reinsmoen & Bach 1983). Many of these HTC-defined HLA-D specificities have been shown by comparative population study to be characteristic of specific racial groups.…”

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confidence: 99%

HLA‐DR2 and DR4 further defined by two new HLA‐D specificities (HTC) derived from Israeli Jewish donors: comparative study in Caucasian, Korean, Eskimo and Israeli populations

et al. 1984

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Two newly-identified HLA-D antigens were characterized by testing selected homozygous typing cells (HTC) against responder panels derived from Caucasian, Korean, Alaskan Eskimo and Israeli Jewish populations. The first specificity, defined by typing cell "AZH", is associated with DR2 haplotypes and is detected primarily in Israelis. The second specificity, defined by HTC "TAS", is associated with DR4 haplotypes and is detected with relatively high frequency in Koreans and Alaskan Eskimos. The data indicate that HTC-AZH and -TAS can be used to identify previously undefined splits or variants of lymphocyte-defined (LD) determinants associated with DR2 and DR4 haplotypes. Further, the study demonstrates the utility of comparative population analysis in identifying and characterizing alleles encoded by the HLA-D region and provides additional evidence of heterogeneity within the family of serologically-defined HLA-DR haplotypes.

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Split of HLA-DRw2 into subtypic specificities closely correlated to two HLA-D products

Cited by 35 publications

References 1 publication

Electrophoretic analysis of human HLA-DR antigens from HLA-DR4 homozygous cell lines: correlation between beta-chain diversity and HLA-D.

Electrophoretic analysis of human HLA-DR antigens from HLA-DR4 homozygous cell lines: correlation between beta-chain diversity and HLA-D.

New HLA‐D Alleles Associated with DRI and DR2

HLA‐DR2 and DR4 further defined by two new HLA‐D specificities (HTC) derived from Israeli Jewish donors: comparative study in Caucasian, Korean, Eskimo and Israeli populations

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