Major histocompatibility complex (MHC) structure and function
- John Vella, MD, FACP, FRCP, FASN
John Vella, MD, FACP, FRCP, FASN
- Associate Professor of Medicine
- Tufts University School of Medicine
The principal antigenic barrier to transplantation is a series of molecules which are polypeptide products of a closely linked cluster of genes known, in humans, as the major histocompatibility complex (MHC) or human leukocyte antigens (HLA) . The MHC is highly polymorphic from individual to individual and segregates in families in a Mendelian codominant fashion.
The following is a general overview of MHC structure and function. Details of MHC use in transplantation are discussed separately. (See "HLA matching and graft survival in kidney transplantation" and "Transplantation immunobiology".)
The genes of the human leukocyte antigen (HLA) locus are located on the short arm of chromosome 6. They encode two distinct classes of cell surface molecules: class I and class II . Class I molecules are expressed on the surfaces of virtually all nucleated cells at varying densities, while class II molecules are more restricted to cells of the immune system, primarily B lymphocytes and monocytes. However, cytokines secreted by lymphocytes and monocytes during immune activation can cause dramatic increases in class II HLA antigen expression, even on cell types that normally have little or no surface expression . (See "Human leukocyte antigens (HLA): A roadmap".)
There are three different class I (HLA-A, -B, -C) and class II (HLA-DQ, -DR, -DP) antigens. Studies in renal transplantation indicate that mismatches at the A, B, and DR loci are associated with worse allograft survival. (See "HLA matching and graft survival in kidney transplantation".)
It is now understood that the principal task of the immune system is to distinguish self from non-self. HLA molecules provide the crucial surface upon which the antigen receptors on T lymphocytes recognize foreign (non-self) antigens. On antigen-presenting cells such as macrophages, class II molecules present antigenic fragments to the CD4+ inducer (or helper) T cells, while class I molecules function at the effector phase of immunity by presenting antigens to CD8+ T cells, which generally have cytotoxic or suppressor function . This process of antigen presentation consists of the binding of a single T-cell receptor to a complex on the surface of an antigen-presenting cell consisting of the MHC molecule and a peptide fragment derived from the foreign antigen (figure 1 and figure 2).
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