Thursday, April 05, 2007

T Cell Maturation

A Physorg article entitled Scientists identify new regulatory mechanism for critical protein signaling domain reveals the potential impact of a small molecule known as IP4 which is involved in the binding of particular proteins to membranes and in the maturation of T cells. From the linked article:

"In findings the authors called "unexpected and striking," the study found that a new regulating messenger IP4, a small soluble molecule, augments the binding of three different PH domain proteins to one of the most commonly recognized membrane lipids, PIP3. The study also showed that inhibiting production of IP4 can result in reduced protein binding to membranes and reduced activation of key signaling molecules in developing T cells, leading to a block of T cell maturation and to severe immunodeficiency in animal models."

Aside from advances in medical treatment that could result from the study, the development of the irreducibly complex signaling pathway connected with T cell maturation is of interest from an ID perspective. The enzyme ItpkB is needed to produce IP4 in mice. The normal development of T cells is disrupted when that enzyme is disabled. T cell development is regulated through signaling. Impaired signaling can lead to the death of T cells. Quoting again from the article:

"Itk is a key activator of another enzyme, PLC g1, in T- cells. PLC g1 is important for signaling in many cells, because it generates the secondary messenger molecules IP3 and DAG (diacylglycerol). We found that ItpkB deficient double positive cells have reduced PLCg1 activity and cannot make normal amounts of DAG. Without the IP4 or DAG messengers, which are essential for positive selection of T cells, these ItpkB-deficient T cells cannot develop into mature, functional cells."

Observe the linkage between biomolecules involved in the T cell maturation function. A study of the origin of pathways to this biochemical complex would be challenging.

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