( A team of Fox Chase Cancer Center scien...)Fox Chase Cancer Center scientists identify immune-system mutation

Kappes' laboratory first discovered the mice with this naturally occurring defect in Fox Chase's laboratory animal facility in 1997. Known as "helper deficient" or HD mice, they are proving to be useful for exploring the pathways of lymphocyte development, according to Kappes.

Helper T cells, so called because they arise from the thymus gland, are essential for combating intracellular viral and bacterial infections (cell-mediated immunity) and also for helping other white blood cells (B cells, derived from bone marrow) generate antibodies against foreign agents that enter the body. Other T cells are known as killer cells because they attack foreign invaders more directly.

"The maturation of T cells involves key branch points at which cells choose one of two different pathways, going on to become helper cells or killer cells," Kappes said. His goal is to understand how T cells specialize to do different jobs.

Commitment to the helper or killer lineages correlates precisely with the restriction of the T-cell receptor toward either class I or class II major histocompatibility complex (MHC) molecules. Most helper T cells carry a surface protein called CD4, which is attracted to class II MHC. Killer cells carry the CD8 protein, attracted to class I MHC. However, the underlying molecular pathways that regulate this process have remained obscure.

"The mutant HD mice are unable to generate mature helper T cells, even though their immature T cells carry the CD4 protein," Kappes explained. "Instead, the mutation redirects them to the killer-cell pathway.

"Our new study identifies this defect as a point mutation in the zinc finge
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Source:Fox Chase Cancer Center