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In this article we will discuss about the major histocompatibility in human body and its classes.
B and T cells contain membrane receptors that react with specific antigenic determinants. B cells are activated by interaction with the antigen either in its dissolved form or while it is still a part of the surface of the pathogen.
In contrast, the T cells of an animal are only activated when the antigen is displayed on the surface of a cell that also possesses markers of the animal’s own identity. These markers are proteins encoded by a cluster of genes called the major histocompatibility complex (MHC) and are called the MHC glycoproteins.
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The MHC glycoproteins were discovered as a result of tissue-transplantation or tissue-grafting experiments. Grafts involving donors and recipients from the same strain of experimental animals (i.e., the equivalent of identical twins) are usually accepted by the donor’s body.
However, when the donor and recipient are not genetically identical, the graft is rejected because the recipient mobilizes an immune response to the transplanted cells and destroys them.
It appears that different (i.e., unrelated) individuals express different sets of MHC genes and like the antibodies and T-cells receptors, these proteins are incredibly diverse. However, unlike antibodies and T-cell receptors, which differ among the millions of different clones of cells of an individual, the MHC proteins differ only among individuals, that is, all cells of a single individual bear the same MHC proteins.
Human MHC proteins are called human leucocyte-associated antigens (since they were first identified in leucocytes or white blood cells) and can be divided into two major classes: Class I MHC antigens and Class II MHC antigens.
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1. Class I MHC Antigen:
They are found on the surfaces of nearly all cells. These antigens consist of two polypeptide chains: a large α chain that is similar in size and organisation to an immunoglobulin heavy chain and a smaller chain called B2– microglobulin.
2. Class II MHC Antigen:
They are not found in the surfaces of all types of cells; rather, they are limited to a few types of cells that play a role in the immune response. For example, they are found in most B cells, some T cells and some antigen-presenting macrophages.
Class II antigens are composed of two polypeptide chains: an alpha chain and a beta chain, each about the same size as an immunoglobulin light chain and play a role in determining the action of T cell.
T Lymphocytes and the Immune Response:
T lymphocytes do not interact with free antigens or with antigenic sites on the surfaces of foreign microorganisms. Instead, T cells respond only to cells bearing both a self MHC antigen and an antigenic determinant from a foreign source (i.e., from bacteria, viruses, etc.).
Thus, two stimuli are needed to trigger the proliferation and terminal differentiation of the required T-cell clones. Cytotoxic T cells respond to the combination of foreign antigen and class I MHC antigens, whereas helper T cells respond to foreign antigen and class II MHC antigens. Thus, the activities of these cells are directed toward the body’s own cells and not to free pathogens.
(i) Cytotoxic T Cells:
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When a virus attacks a cell, the viral nucleic acid enters the host cell, and proteins (antigens) of the viral coat remain at the cell’s surface: Consequently, the infected cell has the proper combination of surface antigens to be recognised by cytotoxic T cells namely, class I MHC antigens and viral antigens.
Thus, cytotoxic T cells attach to newly infected host cells, killing them before virus replication occurs. A number of host cells are necessarily killed by this process before the virus infection is reduced. A single cytotoxic T cell may kill several host cells. Both the viral antigen and the class I MHC antigen are involved in attachment of the T cell.
Binding to the target stimulates these cytotoxic cells to release pore-forming protein called perforins, which polymerise in the plasma membrane of target cell to form transmembrane channels. By causing the membrane to become leaky, the channels are believed to help kill the cell.
(ii) Helper T Cells:
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Macrophages and other scavengers ingest and degrade foreign antigens, ultimately displaying their antigenic determinants at the cell surface. The combination of antigenic determinant and class II MHC antigens at the surfaces of these cells leads to the attachment and activation of helper T cells.
Helper T calls can activate B lymphocytes and other T cells (e.g., cytotoxic and suppressor T cells). Certain helper T cells secrete lymphokines or interleukins (e.g., ILs such as IL-1, IL-2…….. IL-6 and gamma interferon); which are substances that activate macrophages and other lymphocytes.
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Some lymphokines attract macrophages to the site of infection. Other lymphokines prevent migration of macrophages away from the site of infection. Still other lymphokines stimulate T cell proliferation.
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The net effect of lymphokine secretion is the accumulation of macrophages and lymphocytes in the region of an infection and is characterised by the inflammation that typically exists there.
Helper T-cells do not confine their help to lymphocytes. Those helper T cells that secrete interleukin-2 (IL-2) when stimulated by antigen also secrete other interleukins such as gamma- interferon that attract macrophages and activate them to become more efficient at phagocytising and destroying invading microorganisms (e.g., tuberculosis bacterium which can survive simple phagocytosis).
(iii) Suppressor T Cells:
The discovery that T lymphocytes can help B cells make antibody responses was followed several years later by the discovery that they can also suppress the responses of B cells or other T cells to antigens.
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Such T cell suppression was first demonstrated in mice that had been made specifically unresponsive (tolerant) to sheep red blood cells (SRBC) by repeated injections of large numbers of SRBC. When T cells from tolerant mice were injected into normal mice, the latter also became specifically unresponsive to SRBC antigens.
This implies that the tolerant state in this case is due to suppression of the response by T cells. Subsequent experiments using surface antigenic markers suggested that cells responsible are a specialised class of T lymphocytes, called suppressor T cells.
Thus, helper T cells act directly on the effector cells (i.e., B cells and cytotoxic T cells) and suppressor T cells are thought to act indirectly by inhibiting the helper T cells on which the effector cells depend, although the mechanism of inhibition is unknown.
T Cell Receptors:
Like the plasma membrane of B cells, T cell surfaces also contain antigen binding receptors. T-cell receptors are a distinct class of proteins which have many properties common with antibodies. The T cell receptor is about two-third the size of an antibody and consists of two subunit polypeptides connected by a disulphide bridge.
One polypeptide is called an alpha chain and the other a beta chain. Each chain is composed of a constant domain and a variable domain. The disulphide bridge that connects α and β chains occurs between constant domains.
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At the end of each constant domain, there is a region rich in hydrophobic amino acids; this region anchors the receptor in the plasma membrane. A typical T cell has 20,000 to 40,000 α/β receptor proteins on its surface.
AIDS (Acquired Immune Deficiency Syndrome):
The most recent dreaded disease of AIDS is caused by a virus called human T-Cell lymphotropic virus-III (or HTLV-III). The HTLV-III is a retrovirus, that is, it is an RNA virus that induces its host cells to proliferate new viral genes by reverse transcription. This virus critically injures the immune system by infecting and eventually killing T cells.
As a result of the progressive destruction of its T cells, the body is easily ravaged by a number of common infectious agents. Unable to battle infections in the normal manner, victims that develop a “full-blown” case of AIDS eventually succumb. In AIDS patients, the HTLV-III virus has been shown to be present in semen as well as in the blood.
