COMBINATORIAL DIVERSITY IN DR2 HAPLOTYPES

Sequence analysis has identified multiple alleles at two loci that enc ode for the DR2 specificity. The loci, DRB1 and DRB5, are in linkage d isequilibrium which can extend to alleles of the DQ loci. Serologic, c ellular, and sequence-specific oligonucleotide probe (SSOP) typing tec hniques have been used to identify the DR2 haplotypes. In this report, we have characterized by SSOP typing and cDNA/DNA sequence analyses t he combinatorial diversity of DR2 haplotypes. Cells were selected on t he basis of unique serologic reactivity, unique associations of allele s of DR and DQ loci, and/or presence in populations which have not bee n extensively characterized for HLA diversity. An asymmetric polymeras e chain reaction (PCR) amplification was applied to rapidly screen uni que cells and to characterize DNA sequence in conjunction with more co nventional cDNA sequence analysis. The sequence data confirm the lack of a DRB5 locus in the DR2''LUM'' specificity, the unexpected associat ion of DRB11602 and DRB5*010 alleles in a nonCaucasoid population, an d the association of the allele DRB11503 with DRB5*0101 in black Afri can, African American and native American individuals. The DRB11503 a nd DRB50101 alleles were identified in an unusual haplotype, DR2,DQ2. The combinatorial diversity of the DR2 haplotypes is extended by thes e studies in nonCaucasoid populations.