Complete analysis of HLA-DQB1 polymorphism and DR-DQ linkage disequilibrium by oligonucleotide typing

HLA class II polymorphism is functionally important in the control of immune responses, in transplantation immunology, and in the suceptibility to autoimmune diseases. HLA-DQA1 and -DQB1 genes exhibit a larger degree of allelic polymorphism than usually recognized by routine serology. We have therefore performed an extensive analysis of DQB1 polymorphism by oligotyping. A set of 12 oligo probes was hybridized on polymerase chain reaction-amplified DNA, thus allowing the detection of 12 DQB1 alleles, as demonstrated in homozygous as well as in heterozygous individuals. This highly sensitive detection system is particularly relevant within the DQw1 specificity where the 7 allelic sequences can easily be identified. The DQ-DR linkage disequilibrium was analyzed by oligotyping of 80 Caucasoid heterozygous individuals (160 haplotypes), and very tight associations were observed between DRB1 and DQB1 alleles. Five DRB1 alleles, DR-BON, DR4/Dw4 or Dw14, DR7, DRw8.3, and DRw11, however, can be associated with different DQB1 alleles. Moreover the DRB1 and DQB1 oligotyping analysis performed on 20 randomly chosen DRw8 Caucasoid individuals showed a high prevalence of the DRB1*0801-DQB1*0402 haplotype. By combining the analysis of allelic variations at DRB1, DRB3, and DQB1 loci, we can detect 33 different DR-DQ combinations in our panel of Caucasoid individuals. We now apply DQB1 oligotyping on a routine basis for optimal matching of unrelated donors for bone marrow transplantation.