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

Abstract

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...

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

“…1). This DQ pattern has always been found in DRw16/DQwl Caucasoid healthy controls (7,22,23). Conversely, no T-cell clone reactivity was observed with DRw1S-positive IDDM APC ( Table 2), indicating that DR and DQ products from DRw15 and DRw16 haplotypes are not functionally related among type I diabetic patients, as previously demonstrated by us with healthy controls (18,19).…”

“…Control healthy individuals refers to a series of nine DRw15/Dw2 or Dw12 or DRw16/Dw21 healthy Caucasoid donors. Each pattern associated with Dw2l, Dw2, and Dw12 (7,22,23) is shown in this figure.…”

Restriction fragment length polymorphism of DQB and DRB class II genes of the ovine major histocompatibility complex

“…Genomic DNA from 89 sheep, digested with five restriction endonucleases (Barn HI, E m RI, Hin dIII, Pvu I1 and Taq I) and successively hybridized to ovine exon2 specific DQB and DRB probes detected 4 1 distinct and clear-cut fragments with the DQB probe (of which three were constant in all 89 animals) and 32 fragments with the DRB probe (of which 12 were constant). The intensity of a band on the autoradiogram allowed its assignment to a specific DQB or DRB fragment (Font et al 1986). For example, the DQB fragments were those detected only with the DQB probe, or those presenting a stronger signal with this probe.…”

A new HTC, a PLT and a PLT clone define a split of HLA‐DR2 in the Austrian population

“…Numerous studies on frequencies and associations of HLA-DR and HLA-D determinants in Caucasian and non-Caucasian populations have shown that serologically defined HLA-DR antigens can usually be subdivided by cellularly defined HLA-D determinants (Grosse-Wilde et al 1984, Layrisse et al 1978, Suciu-Foca et al 1981, Amar et al 1982, Duquesnoy et al 1984. In addition to the officially recognized cellular splits of the antigens HLA-DR2, DR4, DRw6 and DR7 (Sasazuki et al 1980, Batchelor et al 1984, Jaraquemada et al 1984, Honeyman et al 1984, more recent studies indicate that fur-* National Tissue Typing Laboratory (Council of Europe) National Blood Group Reference Laboratory (WHO) ther LD defined splits of HLA-DR specificities exist (Font et al 1986, Bach et al 1987, Bidwell et al 1986, Hajek-Rosenmayr et al 1986). Biochemical and moleculargenetic analysis of HLA-DR antigens and their HLA-D splits in general have confirmed these results, showing that polymorphisms of DR, of DR and DQ polypeptide chains and DQ polypeptide chains contribute to the generation of HLA-D haplotypes recognized by cellular reactions (David et al 1983, Nepom et al 1983, Nepom et al 1984, Haziot et al 1985, Baldwin et al 1985, Karr 1986, Bosch et al 1987.…”