Human Leukocyte Antigen (HLA)

The human leukocyte antigen (HLA) is not a single antigen, but is rather a group of proteins that are located on the surface of white blood cells. These proteins have a pivotal role in the body's immune response to foreign material. Because the HLA is a chemical tag that distinguishes "self" from "nonself," the antigen is important in the rejection of transplanted tissue and in the development of certain diseases (e.g., insulin-dependent diabetes).

The HLA is the human version of a complex that is known as the major histocompatibility complex. Similar complexes exist in other species. Indeed much of the early knowledge of the antigen complex came from work on mice in the early decades of the twentieth century. Research on human blood cells in the 1950s identified three genes associated with the HLA (HLA-A, HLA-B, HLA-C). In the 1970s, another gene was identified (HLA-D). With the advent of molecular technology beginning in the 1980s, more genes that code for proteins that function in the antigen complex have continued to be identified.

The HLA evolved to serve two functions. The first is to chemically label a cell in a manner that is unique to that cell. White blood cells from all but an identical twin will have differently structured HLAs on their surface. Thus, if white blood cells from one person are injected into someone else, the injected cells will be recognized as foreign. This recognition occurs because the HLA groups are "read" by an immune cell called the T cell. Essentially the different HLA arrangement on cells allows the immune system to develop an inventory of "self" antigens in the body. Knowing the "self" antigen allows the immune system to rapidly distinguish foreign antigens.

HLAs are a class of what is referred to as the major histocompatibility complex. These molecules are made up of a portion that is embedded in the cell membrane and a portion that protrudes out from the membrane's outer surface. The molecules function to identify a cell to the T lymphocyte cells of the immune system. The T cell will recognize a region of the histocompatibility complex as a host structure, and no immune reaction will be initiated towards the cell. In another host, the same region could be recognized as foreign by the T lymphocytes.

HLA-D is a so-called class II major histocompatibility molecule. Class II molecules have two segments that are embedded in the membrane. At the outer surface of the cell the molecule contains an antigen that has been acquired from the surrounding environment. Particles are engulfed, broken down into their constituent parts, and some of the components end up incorporated into the class II histocompatibility complex. Thus phenomenon is referred to as antigen presentation.

Class II molecules are not present on all cells the way class I molecules are. Rather, class II molecules are on the surface of immune cells such as macrophages and B-lymphocytes that are designed to process cells and present the antigens from these cells to T lymphocytes. This is done to increase the repertoire of antibodies that an organism possesses.

The two classes of histocompatibility molecules allow an organism to in essence establish an inventory of what cells are "self" and to expose foreign antigens to the immune system so that antibodies to these antigens can be made. In the future, an invading organism that possesses one or some of these "non-self" antigens will be swiftly recognized as an invader and will be dealt with.

Defects in the structure of the HLAs is the cause of some diseases where the body's immune system perceives a host antigen as foreign and begins to attack the body's own tissue. An example is insulin-dependent diabetes, where a host immune response causes the destruction of insulin producing cells.

See also Histocompatibility; Immune system; Immunodeficiency diseases