[Current approach to HLA typing for bone marrow transplantation: oligonucleotide typing by hybridization on DNA amplified by polymerase chain reaction]

Abstract

The extensive polymorphism of major histocompatibility complex HLA class II antigens plays a crucial role in transplantation immunology. The molecular biology of the HLA-D region has revealed that the polymorphism at the HLA-DR, -DQ and -DP loci is much greater than was expected from serology, and thus requires accurate typing technology. We have shown that HLA class II polymorphism can be analyzed directly at the DNA level by hybridization with locus- and allele-specific oligonucleotide probes (oligotyping) derived from the variable first domain exon sequences of DR, DQ and DP genes. The same HLA typing procedure can be performed by direct hybridization on DNA previously amplified by the polymerase chain reaction (PCR). Here we show that oligotyping can complement and/or replace serological as well as cellular (Dw) typing and serves to predict a positive mixed lymphocyte culture. It is now operational (a) to replace serology when class II expression is absent or aberrant (e.g. leukemic patients, class II deficiencies) and (b) to improve, by the analysis of HLA-DR and -DQ micropolymorphism, the speed and reliability of the selection of optimally-matched unrelated donors for bone marrow transplantation.