Enzyme keeps immune system in check - Baylor College of Medicine

November 22, 2006

Enzyme keeps immune system in check

HOUSTON -- (November 19, 2006) -- Until Dr. Tse-Hua Tan studied mice

that lacked the enzyme hematopoietic progenitor kinase 1 (HPK1), he

thought the molecule – discovered in his laboratory a decade ago –

increased the activity of the immune system.

To the surprise of the Baylor College of Medicine professor of

immunology, when there was no HPK1 in the animal's cells, signaling

that marshaled the immune system forces called T-cells was enhanced

as was cellular proliferation. In fact, the protein did the opposite

of what he expected – it slowed or decreased immune action.

" This finding indicates that HPK1 negatively regulates signaling

directed at T-cells and T-cell proliferation, " said Tan. A report of

the work carried out in his laboratory appears online today in the

journal Nature Immunology.

In fact, he said, mice that lacked this important enzyme were more

susceptible to a form of autoimmune disease that mimics multiple

sclerosis.

" This is consistent with the possibility that this protein plays a

role in preventing autoimmune disease, " he said.

In fact, he said, HPK1's strength in that role may occur because it

actually affects two molecules with activity that occurs early in the

cascade of events that result in activation of T-cells. By affecting

these molecules, it intervenes early in the process of lymphocyte or

T-cell activation and is more effective, said Tan.

While T-cell activity is critical in defending the body against

invading bacteria and other organisms, it is also important to shut

that activity off when it has accomplished its task and before it

starts to attack the body's own tissues, said Tan. HPK1 appears to

play a role in halting the T-cell action.

Others who took part in the research include: Drs. Jr-Wen Shui,

S. Boomer, Jin Han, Jun Xu, A. Dement and Guisheng

Zhou, all of BCM.

Support for this work came from the National Institutes of Health and

the American Heart Association Texas Affiliate.

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