Primary immunodeficiency diseases are unique human models to study the molecular events that ultimately lead to an efficient immune response. With the support of this grant, this group has participated in the identification of genes involved in X-linked immunodeficiency diseases and in the functional analysis of the products of these genes. The understanding of the molecular basis for immune disorders has contributed greatly to the concept of receptor-ligand interaction, and the principles of lymphocyte activation, differentiation, signal transduction and immunoglobulin isotype switching. The principal investigator has been part of a team that recently isolated the gene mutated in patients with the Wiskott- Aldrich syndrome (WAS), a disorder in which most hematopoietic cell lineages are affected.The investigator's collection of B-cell and T-cell lines derived from members of over 25 affected families will permit a representative mutation analysis of WAS and will answer the question of whether a correlation exists between clinical phenotype and type of mutation. Based on the amino acid composition derived from the known cDNA sequence, the investigators have outlined strategies to analyze the nature of the WAS protein. The principal investigator will focus on WAS gene expression and its control, the physical and functional properties of the WAS protein, its distribution within the cell, and its phosphorylation state.
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