Last updated: 11/24/2009

The HLA gene products can be grouped into three classes. Class I consists of the products of the genes located on the HLA-A, HLA-B, and HLA-C loci. These HLA antigens are found on all nucleated cells. Class II molecules consist of antigens inherited as genes from the HLA-DR, HLA-DQ, and HLA-DP loci. These HLA antigens are normally found only on B-lymphocytes, macrophages, monocytes, dendritic cells, endothelial cells, and activated T-lymphocytes. Class III molecules are not evaluated in histocompatibility testing.

Because the HLA loci are closely linked, the HLA antigens are inherited as a group of six antigens is called a haplotype. The probability of siblings having identical haplotypes is one in four. Therefore, siblings provide the opportunity for the best matches. They can donate bone marrow, a kidney, and a section of their livers, but they cannot donate other solid organs. Approximately 85% of transplants are organs from cadavers, and because the HLA antigens are so highly polymorphic, the chance of identical haplotypes decreases quickly.

Histocompatibility testing consists of three tests, HLA antigen typing (tissue typing), screening of the recipient for anti-HLA antibodies (antibody screen), and the lymphocyte crossmatch (compatibility test). HLA antigen typing may be performed by serological or DNA methods.

A laboratory will perform HLA typing by either the serological (blood fluid) or DNA method. In either case, HLA typing of HLA-A, HLA-B, HLA-DR, and HLADQ antigens is performed for solid organ transplants. HLA typing of HLA-C antigens is also included when tissue typing is performed for bone marrow transplants.

The antibody screen is performed in order to detect antibodies in the recipient's serum that react with HLA antigens. The most commonly used method of HLA antibody screening is the microcytotoxicity test. If an antibody against an HLA antigen is present, it will bind to the cells. The higher the number of different HLA antibodies, the lower the probability of finding a compatible match.

The third component of a histocompatibility study is the crossmatch test. In this test peripheral blood lymphocytes from the donor are separated into B and T lymphocyte populations. In the crossmatch, serum from the recipient is mixed with T-cells or B-cells from the donor. A positive finding indicates the presence of preformed antibodies in the recipient that are reactive against the donor tissues. An incompatible T-cell crossmatch contraindicates transplantation of a tissue from the T-cell donor.