Serologic and molecular studies of two kindreds expressing recombinant HLA DR1/DR2 haplotypes

We have recently identified two unrelated kindreds in which DR1 and DR2 co-segregate as a single haplotype spanning several generations. Serology, PCR-RFLP and sequence-specific oligonucleotide probes were used to characterize the presence and segregation of the DRB1 and DRB5 loci in these two kindreds. In both families, the recombination resulted in co-expression of a DRB1 locus that encoded a DR1 serologic phenotype and a DRB5 locus that encoded a 'short' DR2 serologic phenotype. One of these kindreds co-expressed the DR1 and DR15 (DRB5(*)01). The other kindred co-expressed the DR1 and DR16 (DRB5(*)02). Our data indicate that the recombination event occurred in the region between the DRB1 locus and the DRB5 locus. This recombinant haplotype produces a DR2 phenotype which lacks the epitopes normally encoded by the DRB1 locus, resulting in a serologic 'short' antigen. The clinical significance of such a recombinational event becomes evident when patients with such a genotype require allogeneic bone marrow transplantation.