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The genetic polymorphism of the HLA-DPB1 and DPA1 loci was studied in 60 unrelated caucasoid individuals by PCR-RFLP. The polymorphic second exon of DPB1, the third exon of DPA1, and the transmembrane DPA1 exon were specifically amplified in vitro by polymerase chain reaction (PCR). Amplified DNAs were digested with selected enzymes. Twenty patterns were obtained with DPB1 defining 20 DPB1 alleles. Thirty-nine homozygous cell lines were used as HLA-DP reference cells. The results obtained with these cell lines were compared to those obtained by PLT, RFLP, and SSO. Although three subdivisions of the allele DPA1*01 were reported, DPA1*0103 was the only represented one in the caucasoid population. In the studied population, it was the most frequent DPA1 allele (76.6%), whereas DPA1*0201 frequency is 23.3%. DPB1*0401 and DPB1*0402 are the most frequent among the DPB1 alleles (40.0% and 13.3%, respectively). This may lead to a lower HLA-DPB1 diversity among caucasoids. Certain HLA-DPB1 alleles associate exclusively with one DPA1 allele (DPB1*0401, 0402, and 0301 with DPA1*01 and DPB1*0101, 0501, and 1701 with DPA1*0201) whereas the others can associate with both DPA1 alleles. This by itself can create another kind of polymorphism, indicating the importance of HLA-DPA1 typing. Thus, PCR-RFLP seems to be one of the best DNA typing methods: it represents direct, accurate, fast, and nonradioactive typing for both HLA-DPA1 and HLA-DPB1 alleles.

Primary Sjogren syndrome (pSS) is an autoimmune disease characterized by progressive destruction of the exocrine glands leading to mucosal and conjonctival dryness. It is marked by lymphocytic infiltration of the glands and the accumulation of several types of autoantibodies such as rheumatoid factor (RF), antinuclear, anti-SS-A (anti-Ro) and anti-SS-B (anti-LA) autoantibodies. The susceptibility to pSS and/or the presence of SS-A/SS-B autoantibodies in pSS patients is associated with DRB1∗03-DQB1∗02 and DRB1∗02-DQB1∗06 haplotypes, whereas no associations have been described with any HLA class I allele. To define the impact of HLA class I alleles in predisposition to pSS, 46 patients responding to the European criteria and 222 healthy unrelated Caucasians were analyzed for their HLA class I and class II haplotypes. Our results confirm the association of the DRB1∗03-DQB1∗02 haplotype with SS-A/SS-B autoantibodies positive pSS and demonstrate a significant association of the HLA-A24 with the disease. Moreover, HLA-A24 is more often associated with DRB1∗11-DQB1∗0301 and/or DRB1∗0301-DQB1∗02 in pSS patients than in the controls. The novel association of HLA class I alleles with susceptibility to pSS provides new insights to the genetic predisposition to this disease and subsequently to its physiopathology.

MS is an autoimmune demyelinating disease that has been known to be associated with the HLA-DRB1∗1501-DQA1∗0102-DQB1∗0602 haplotype. TAP1 and TAP2, two genes encoded within the MHC class II region between HLA-DP and -DQ loci, display genetic variability and are involved in the transport of antigenic peptides from the cytoplasm to the endoplasmic reticulum. Comparison of 116 MS patients with Caucasoid controls did not reveal any significant correlation between the previously described alleles of the TAP1 and TAP2 genes and MS. We report here an additional TAP2 dimorphism at codon 386, called I and J, corresponding to a silent mutation. An increased frequency of the J variant was observed in the patient population. The J mutation was not found in linkage disequilibrium with the HLA-DRB1∗1501 allele and can be considered an additional genetic susceptibility marker of the disease.

Seven groups, each consisting of two to nine unrelated HLA-A, -B, and -DR serologically identical individuals, were analyzed by DNA-restriction fragment length polymorphism (RFLP) and mixed lymphocyte reactions (MLR) in order to evaluate HLA-class II identity between unrelated individuals and to assess the importance of HLA-class II incompatibilities detected by DNA-RFLP in the allogeneic reactions. It is clear that DNA-RFLP represents a powerful typing method for HLA-DR, -DQ, and -DP since the combinations of the RFLP band patterns define all the serological specificities and most of the cellular specificities to give a highly accurate typing. This report shows that an HLA-DP incompatibility induces proliferation in primary mixed lymphocyte culture (MLC) between unrelated HLA-A, -B, -DR, -DQ, and -DW identical individuals, which may suggest the importance of this molecule as a transplantation antigen, especially for unrelated bone marrow transplantations. Still, an isolated HLA-DPw4/HLA-DP a disparity did not induce any proliferation in MLC. Moreover, our results show that DQw7 (w3)/DQw8 (w3) disparity associated with HLA-DR4 represents a nonfunctional incompatibility in MLR. The HLA-Dw subtypes of HLA-DR specificities can induce a high proliferative response in MLC. The HLA-Dw subtypes of HLA-DR specificities can induce a high proliferative response in MLC. Finally, DNA-RFLP typing represents a reliable method for the selection of histocompatible donor-recipient pairs and could potentially reduce many logistic problems and delays in live-donor transplantation, especially for unrelated bone marrow transplantation.