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Human Genome News, July 1994; 6(2)
Much research has been devoted to studying genes and protein products of the human major histocompatibility complex, which occupies a 4-Mb stretch on the short arm of chromosome 6.
Residing in this area are genes responsible for cellular immunity--one of two main defenses evolved by vertebrates in their constant struggle to defend the body against the steady stream of microorganisms (viruses, bacteria, and other pathogens) that invade it. The body's other main defense is humoral immunity, which involves protein antibodies that are released into extracellular fluids and blood to fight foreign invaders.
Cellular immunity is based on the interaction of MHC proteins found on surfaces of circulating cells and T lymphocytes (white blood cells that pass through the thymus gland during maturation). Produced in cells' endoplasmic reticulum, MHC proteins act as sentries in the war against intruders, recognizing them and identifying infected cells for destruction by specialized T cells. MHC proteins accomplish this task by capturing pieces of foreign proteins (peptides) they find within an infected cell and transporting them to the cell's surface. The MHC-foreign peptide complex is then recognized and bound by surface molecules (T-cell receptors) found on "killer" T cells.
MHC proteins also promote the release of lymphokines by "helper" T cells. Lymphokines stimulate the body's overall immune response, including B-cell antibody production and activation of macrophages and other cells that participate in immune reactions. Loss of helper T cells, as occurs in HIV infection, results in immune-system failure.
The ability to distinguish normal body constituents ("self") from everything else ("nonself") is based on individual differences in MHC proteins. When MHC genes were first cloned, researchers discovered that these proteins are exactly the same from cell to cell in each individual but differ markedly among people, more so than with most other proteins. In humans, genes encoding proteins for self recognition are designated HLA (for human lymphocyte antigen). Scientists screening organ donors attempt to minimize the potential for rejection by matching patients with donors having the most-similar HLA proteins.
Immune-system failures lead to loss of immune function, tumors, hyperreactive conditions such as allergies, and autoimmune diseases such as arthritis and type 1 diabetes. Auto-immune diseases occur when the immune system mistakes the body's own proteins for intruders and marks healthy cells for destruction.
Researchers expect that a better understanding of how the MHC-foreign peptide complex binds to the T-cell receptor will one day lead to the development of new ways to fight transplant rejection and infectious and autoimmune diseases. These might include drugs that block binding sites or engineered receptors that can recognize features of pathogens with greater accuracy.
With 100 mapped genes, the human MHC is one of the most- detailed areas of the human genome map. It is divided into three regions: class I (the 2-Mb telomeric region), class II (the 1-Mb centromeric region), and class III (the intervening megabase). The entire MHC has been cloned in YACs, and most regions are also represented in overlapping cosmid clones. Availability of these resources has led to the recent initiation of large-scale projects to sequence the MHC and to centralize much of the mapping and sequencing data in the MHC database. [Denise K. Casey, HGMIS]
The electronic form of the newsletter may be cited in the following style:
Human Genome Program, U.S. Department of Energy, Human Genome News (v6n2).
The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.
Published from 1989 until 2002, this newsletter facilitated HGP communication, helped prevent duplication of research effort, and informed persons interested in genome research.
