Learn the organization of human leukocyte antigen (HLA) genes and the molecular details of their gene products.
Understand the clinical laboratory tests used to assess histocompatibility.
Learn the histocompatibility requirements for the solid organ and stem cell transplants in clinical use.
An animal will generally accept an organ transplant from itself, but will reject a transplant from other animals, even if the donor animal is of the same species. Organ rejection is primarily a consequence of the interactions between the immune system of the transplant recipient and the histocompatibility antigens present on the transplanted cells. Clinical laboratories play an important role in the histocompatibility testing for solid organ as well as hematopoietic stem cell and bone marrow transplantation (BMT). This chapter provides a brief background to some of the issues and techniques involved in histocompatibility testing related to transplantation. Other applications of histocompatibility testing such as in the characterization of disease states (eg, HLA-B27 in ankylosing spondylitis) or before initiation of some drug therapy (eg, HLA-B*57:01 is a risk factor for hypersensitivity to abacavir) use similar techniques and are not discussed further.
The histocompatibility antigens that are the primary stimulus in graft rejection are encoded by a complex of closely linked genes called the major histocompatibility complex (MHC). In mice, these genes are located on the H2 region of chromosome 17. In humans, the analogous MHC region is located in a 4000-kb region on the short arm of chromosome 6 and encodes for the HLA system (Figure 4–1).
Genes of the human MHC system. The human major histocompatibility complex (MHC) is located on the short arm of chromosome 6. It contains over 200 genes that can be divided into different regions (class I-III). Only the major genes encoding the HLA molecules important in transplantation are shown. The class I region contains genes that encode the α chains of the classic transplantation antigens, HLA-A, -B, and -C. The class II region has genes that encode both the α and β chains of HLA-DP, -DQ, and -DR molecules. Genes encoding the α and β chains are designated as “A” or “B,” and are followed by a number if there is more than 1 gene encoding a particular chain or a related pseudogene. For example, DRB1 is 1 of the genes that encodes the β chain of DR molecules. The class III region is located between regions I and II and does not encode for HLA molecules. (Adapted with permission from Clinical Laboratory Reviews [a newsletter publication of the Massachusetts General Hospital] 2000;8:3.)
HLA Genes and Gene Products
The HLA class I region encodes for certain glycoprotein molecules that are present on all nucleated cells. The main function of the HLA class I molecules is to ...