Allergic diseases, autoimmune diseases and immunodeficiency syndromes can be viewed as diseases that affect T-B cell interactions and antibody production. A molecular understanding of the processes involved in T and B cell activation is essential for accurate diagnosis and therapy of allergic and immune diseases. In this AAIDCRC, we propose to continue to investigate the mechanisms of B cell activation and isotype switching and the molecular basis of immunodeficiency disease, and MHC class II deficiency, that affects T cells and impairs the capacity of B cells to mount an antigen specific antibody response. For this purpose, we recently acquired knowledge of isotype switching and of the molecular composition of the B cell antigen CD4O to study B cell activation; we will take advantage of recent discoveries of the defective genes in MHC class Il deficiency to gain a better understanding of the molecular basis of these diseases. Definition of the DNA sequences and factors that are critical for isotype switching (Project #1, F. Alt) and molecular analysis of the CD4O receptor. complex (Project #2, R. Geha) will permit a better understanding of allergic diseases. Elucidation of the mechanisms of activation of MHC class Il gene transcription by products of genes that are mutated in MHC class II deficient patients (Project #5, L. Glimcher) has important applications to the control of MHC class Il expression in autoimmune diseases. An asthma education and demonstration program will assess the impact of education on asthma mortality and morbidity in hispanic inner city children. The results of the proposed studies will enhance our understanding of immune function and help devise rational therapeutic interventions for allergic and immunologic diseases.
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