Major Histocompatibility Complex Genes

When tissues are transferred from one species to another or even from one individual member to another within a species, the transplanted tissues are usually rejected by the host animal. The results of early studies demonstrated that this graft rejection is due to an immune response that occurs when antigens on the surface of the grafted tissue are detected and attacked by T cells in the host organism. The antigens that elicit graft rejection are referred to as histo-compatibility antigens, and they are encoded by a cluster of genes called the major histocompatibility complex.

T cells are activated only when the T-cell receptor simultaneously binds both a foreign antigen and the host cell's own histocompatibility antigen. The reason for this requirement is not clear; it may reserve T cells for action against pathogens that have invaded cells. When a foreign body, such as a virus, is ingested by a macrophage or other cell, partly digested pieces of the foreign body containing antigens are displayed on the macrophage's surface (I Figure 21.21). Through their T-cell receptors, T cells bind to both

Macrophage

Virus

MHC molecule

^ A virus is ingested by a macrophage,.

Viral (foreign) antigen

^ .which processes and displays foreign antigens on its cell surface.

ft A T-cell receptor binds the foreign antigen and the host cell's own histocompatibility (MHC) molecules.

Macrophage

Virus

MHC molecule

^ A virus is ingested by a macrophage,.

^ .which processes and displays foreign antigens on its cell surface.

Viral (foreign) antigen ft A T-cell receptor binds the foreign antigen and the host cell's own histocompatibility (MHC) molecules.

^This binding stimulates the T cell to release perforins.

.that lyse the antigen-presenting cell.

^This binding stimulates the T cell to release perforins.

.that lyse the antigen-presenting cell.

121.21 T cells are activated by binding to a foreign antigen and a histocompatibility antigen on the surface of a self-cell.

the histocompatibility protein and the foreign antigen and secrete substances that either destroy the antigen-containing cell or activate other B and T cells or both.

The MHC genes are among the most variable genes known: there are more than 100 different alleles for some MHC loci. Because each person possesses five or more MHC loci and because many alleles are possible at each locus, no two people (with the exception of identical twins) produce the same set of histocompatibility antigens. The variation in histocompatibility antigens provides each of us with a unique identity for our own cells, which allows our immune systems to distinguish self from nonself. This variation is also the cause of rejection in organ transplants.

www.whfreeman.com/pierce Additional information about the genetics of the immune system

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