A possible new HLA-DR allele

Bétuel, H; Gebuhrer, L.; Lambert, J.; Freidel, A. C.; Farre, Annie

doi:10.1016/0198-8859(83)90040-x

Cited by 37 publications

(14 citation statements)

References 10 publications

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“…The 24 selected cells have been typed for HLA-A, -B, -C, -DR, -DQ, and -D by methods already described (8) with local and 9th Histocompatibility Workshop reagents. Sixteen cells were homozygous for HLA-Dw, eight were heterozygous (see Fig.…”

Section: Methodsmentioning

confidence: 99%

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HLA-DR2, -DR5, and DRw6 associated Dw subtypes correlate with HLA-DR beta and -DQ beta restriction fragment length polymorphisms.

Font¹,

Gebuhrer²,

Bétuel³

et al. 1986

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

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DNAs extracted from peripheral blood leukocytes of 24 individuals, selected for their HLA-DR types, -DR2, -DR5, and -DRw6, were analyzed with four restriction enzymes, BamHI, EcoRV, HindIll, and Taq (al, a2) and 2(3 ((31, /32). In addition DZa and DO/3 genes have been characterized but not yet located (2, 3). The numerous antigens encoded by these loci were initially characterized by alloantisera against DR and DQ, homozygous typing cells (HTC), and by primed lymphocytes for D and DP determinants.The specificities recognized by T-cell proliferation in response to allogeneic stimulation by B cells were initially thought to be controlled by the HLA-D locus (4). When serological methods allowed the recognition of B-cell antigens coded by the HLA region, these antigens were correlated with their cellular counterpart. The similarity was sufficient to warrant the existence of DR locus (D related), and the same nomenclature was applied to the specificities defined by two different procedures (5). Subsequently, this position was no longer tenable as new D specificities had no DR equivalent or were included in broader DR reagents. With this approach, it was demonstrated that HTCs typed as DR4 could be resolved in five different clusters by the level oftheir proliferative response when tested against each other (6). Availability of proper alloantisera can lead to the recognition of some Dw types by serology. For example, subtypes of DR2, such as FJO or AZH defined by HTCs, can be serologically recognized (7). An alloantiserum has permitted the distinction of a variant of DRw6 (now DRw14) corresponding to Dw9 (8). However, there still remain Dw subtypes like Dw18 and Dwl9 (subtypes of Dw6), which evade serological recognition. Alleles at the DQ locus (formerly MB) are found in strong linkage disequilibrium with DR antigens. DQwl is usually associated with DR1, DR2, DRw6 (DRw13 and DRw14), and DRw10; DQw2 with DR3 and DR7; DQw3 with DR4, DR5, and DRw9 (20). The rare associations such as DRw13-DQw3 and DRw14-DQw3 raise different cellular response(s) when compared to DRw13-DQwl or DRw14-DQwl. This dissociation has led to the assumption that Dw specificities could correspond to the summation of epitopes present on DR, DQ, and other molecules (9).The obtention and use of class II cDNA probes represent an approach to unravel the complexity of this region through restriction fragment length polymorphism (RFLP) studies (10, 11). The degree of polymorphism depends on the locus explored. Almost no polymorphism was observed for DRa; limited polymorphism was noted for DXa, DPa, and DP/3; in contrast DRf3, DQa, and DQP3 yielded extensive polymorphism (3,12). Generally, the majority of RFLPs correlate with supertypic specificities whereas fewer fragments are found with single DR specificities (12,13). Nevertheless, RFLPs specific for DR-associated subtypes have been reported (3,11,13,14). The aim of the present study was to investigate DRI and DQP RFLP in various subtypes of HLA-DR2, -DR5, and -DRw6. These subtypes selected f...

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Section: Methodsmentioning

confidence: 99%

“…For example, subtypes of DR2, such as FJO or AZH defined by HTCs, can be serologically recognized (7). An alloantiserum has permitted the distinction of a variant of DRw6 (now DRw14) corresponding to Dw9 (8). However, there still remain Dw subtypes like Dw18 and Dwl9 (subtypes of Dw6), which evade serological recognition.…”

mentioning

confidence: 99%

HLA-DR2, -DR5, and DRw6 associated Dw subtypes correlate with HLA-DR beta and -DQ beta restriction fragment length polymorphisms.

Font¹,

Gebuhrer²,

Bétuel³

et al. 1986

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

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“…PBM were isolated as previously described (17) from healthy donors and from four DR2 (DRw15 or DRw16)-positive diabetic patients and six of their first-degree relatives, allowing clearcut haplotype assignment. HLA serological phenotyping was performed with Ninth Histocompatibility Workshop and local reagents according to standard procedures (20). Cellular HLA-Dw typing was performed by testing PBM reactivities against a panel of homozygous typing cells as previously described (21).…”

mentioning

confidence: 99%

HLA-DQ rather than HLA-DR region might be involved in dominant nonsusceptibility to diabetes.

Sterkers

Zeliszewski²,

Chaussée³

et al. 1988

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

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Since HLA-DRw15 (a subdivision of the HLA-DR2 specificity previously called DR2 long) is associated with dominant nonsusceptibility to insulin-dependent diabetes mellitus (IDDM), while HLA-DRw16 (another subdivision of HLA-DR2, previously called DR2 short) is positively associated with the disease, we looked for particular characteristics of An increased frequency of some HLA-DR specificities has been reported among patients with insulin-dependent diabetes mellitus (IDDM): DR3, DR4, and, to a lesser extent, DR1, DRw13, and DRw16 (the last being a subdivision of DR2 previously called DR2 short, AZH, or FJO)II (1)(2)(3)(4)(5)(6)(7)(8). In contrast, an extremely decreased frequency is observed for the DRw15 specificity (a subdivision of DR2 previously called DR2 long)11 (1,9, 10). Because of an aberrant expres-

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“…HLA typing was initially carried out on PBL, T-cell clones, and EBV-transformed B-cell lines using a previously described cytotoxicity assay [14] and was confirmed more recently using molecular biological methods.…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

Transplantation Tolerance Induced in Humans at the Fetal or the Neonatal Stage

Touraine

Sanhadji

2011

Journal of Transplantation

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Patients transplanted with HLA-mismatched stem cells from fetal livers develop transplantation tolerance to donor antigens. Engraftment needs no conditioning regimen prior to transplantation in neonates with severe combined immunodeficiency disease or in human fetal patients having not yet developed any immune maturity, especially T-cell differentiation. The chimeric patients have donor-derived T lymphocytes which progressively demonstrate positive interactions with other host cells. They also can be shown to be tolerant toward both host and donor antigens. The latter tolerance relies upon clonal deletion from the T-cell repertoire, and it results from the contact between thymocytes of donor origin and dendritic cells or macrophages also deriving from donor stem cells. The former tolerance does not imply clonal deletion of T-cells with host reactivity. Numerous T-cells recognizing the allogeneic, host-type antigens are identified in these patients, but these cells are anergized, following interaction with epithelial cells of the host thymus. Induction of transplantation tolerance at the fetal stage requires minimal engraftment only; in the future it will be possible to further amplify the clinical benefit, using additional cell transplants after birth.

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A possible new HLA-DR allele

Cited by 37 publications

References 10 publications

HLA-DR2, -DR5, and DRw6 associated Dw subtypes correlate with HLA-DR beta and -DQ beta restriction fragment length polymorphisms.

HLA-DR2, -DR5, and DRw6 associated Dw subtypes correlate with HLA-DR beta and -DQ beta restriction fragment length polymorphisms.

HLA-DQ rather than HLA-DR region might be involved in dominant nonsusceptibility to diabetes.

Transplantation Tolerance Induced in Humans at the Fetal or the Neonatal Stage

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