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The Past, Present and Future of HLA Typing


The Human Leukocyte Antigen (HLA) region, located on the short arm of chromosome 6 (6p21.3), is a highly polymorphic region containing about 200 genes. The HLA region is the human equivalent of the Major Histocompatibility Complex (MHC), and as such contains a set of genes that serve as the backbone of antigen presentation. The Class I proteins, classically involved in presenting endogenous antigens to CD8+ T-cells, are expressed by genes located in the HLA-A, -B and C loci. In contrast, the Class II proteins, which associate with and present exogenous antigens to CD4+ T-cells, are expressed by the HLA DR, -DQ and DP loci. Each locus is highly polymorphic; for example, there appear to be 300+ alleles in the HLA-B or DRB1 loci. A clear understanding of the differences between HLA polymorphisms has provided ample insight into why and how foreign tissue is rejected by the host, and as such been a critical enabler of the field of transplantation. Today, a variety of techniques are applied for HLA tissue typing, providing an important tool to increase the success rate of human transplants.

For many years, HLA polymorphisms were typed by serological responses HLA antigens; sera containing antibodies to Class I and II proteins were collected from multiparous women, or individuals who had received multiple blood transfusions. In addition, polymorphisms in Class II proteins were analyzed by T-cell responses in the Mixed Lymphocyte Reaction (MLR). However, the advent of recombinant DNA technology, which paved the way to identifying genetic differences among the HLA loci directly, has led many laboratories to abandon classic serological typing methods. Today, several different types of HLA DNA typing methods exist and are commonly used by clinical laboratories. In general, HLA DNA can be typed either by hybridizing labeled, sequence specific oligonucleotide probes to HLA loci amplified by the polymerase chain reaction (PCR), or by using PCR to amplify th
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