History and Naming of Human Leukocyte Antigens

History And Naming Of Human Leukocyte Antigens

Human leukocyte antigens (HLA) began as a list of antigens identified as a result of transplant rejection. The list, HL-A1 to HL-A15. The antigens were identified based on serotypes that developed in transplant recipients, to donor antigens that could recognize one apparent antigen were found useful. HLA are not typical antigens, like those found on surface of infectious agents. HLA antigens are alloantigens, meaning they are due to the genetic differences between individuals, allo meaning different.

A person can have 2 antigen proteins per genetic-locus (one gene from each parent). During development the immune system determines these two antigens are 'self'-antigens or (autoantigens) and turns off the destructive response. However when tissues are transferred to another person they often become alloantigens. Identified antigens can therefore be clustered, creating groups in which no more than two antigens per cluster are found in a given person. Serotype group "A" consisted HL-A1, A2, A3, A9, A10, A11. Another cluster, "B", contained A7, A8, A12, A13, A14, A15. HL-A4 antigen was found to occur on lymphoid cells. Since the "HL-Antigens" no longer belonged to a single group, they were partially renamed. For example "HL-A7" became HLA-B7 and "HL-A8" became HLA-B8.

In this arrangement there were cells that were 'blank' or had new specificities, these new antigens were called "W" antigens, and as they were reassigned to new groups, for example "A" serotypes, they became Aw or Bw antigens. It was found that some antigens that behaved like A and B antigens but could be excluded based on '2-type max' exclusion. Thus a new group, "C" was created. Classification of C antigens is still ongoing, and they have retained the name Cw as many serotypes have not been developed.

The classification of the "A4" antigens was complicated. The "A4" subset evolved to become D-region antigens, which was a large cluster of genes that encoded MHC class II. Several renamings occurred. The D-region has 8 major coding loci that combine to form 3 different protein groups; DP, DQ, and DR. DRw antigens were the first to be split, a process made easy by the virtue of having an invariant alpha chain, but complicated by 4 beta chain loci (DRB1, DRB3, DRB4, and DRB5). Serotypes to DQ reacted with alpha and beta chains, or both of certain isoforms. The proper classification was greatly aided by gene sequencing and PCR. Classification and description of DP antigens is ongoing.