HUMAN LYMPHOCYTE ANTIGEN TYPING - DIRECT DNA TYPING - THE ONLY CHOICE

Exact human lymphocyte antigen (HLA) allele matching and sequence vari ation are important for matching organ donors, immune response studies , and disease association investigations. The number of HLAs has reach ed several hundred within each of the different classes. This level of heterogeneity makes routine DNA typing to the allele level problemati c using fixed probe and primer technologies. Routine large-batch scree ning programs where only intermediate-level typing is required can be performed in automated fashion by several DNA technologies. Screening large numbers of samples with probe-based technologies, even oligo arr ay chips, is cost effective. Allele-specific typing is most easily per formed using direct sequencing. New sequencing technologies based on c ycle sequencing and high-speed capillary gels have made routine sequen cing for clinical typing a reality. The complexity of the class I locu s requires a detailed analysis of all the polymorphisms within exons 2 and 3. Sequencing strategies are thus designed to use informative var iable regions within the flanking introns and the flanking region as w ell as the untranslated regions. Similar strategies are being adapted to the complex class II DRB alleles, which now number about 200 differ ent alleles. Greater understanding of HLA diversity and distribution t hroughout humans and their relatives facilitates organ matching and th e history and origins of human populations. Knowledge of parasites and their role in the selection of alleles will ultimately lead to better prediction and manipulation of the immune system response to these or ganisms. HLA typing is used to determine relative risk to a variety of autoimmune diseases. Future uses of molecular HLA typing may include the prevention and cessation of these self-destructing diseases.