Our past studies related to this grant have shown that murine gut- associated lymphoreticular tissue (GALT), e.g., Peyer's patches (PP), contain a unique subset of T helper (Th) cells which expresses Fc receptors for IgA (FcalphaR) and preferentially collaborate with surface IgA positive (sIgA+)-committed B cells for subsequent IgA antibody synthesis. We have generated T-T hybridomas by fusion of cloned FcalphaR+ PP Th cells with a T lymphoma cell line. Several T cell hybridomas express FcalphaR and secrete IgA binding factor (IBFalpha) which regulates antigen- dependent IgA responses. These studies have shown that FcalphaR Th cells and secreted IBFalpha play an important role in isotype-specific immunoregulation. The overall goal of this grant renewal will be to better understand the precise cellular and molecular events involved in FcalphaR+ Th cell and IBFalpha regulation of IgA responses. Two broad objectives are proposed: 1) to define the molecular relationship between the FcalphaR and IBFalpha, and 2) to study the possible association between the T cell receptor (TCR) for antigen and the FcalphaR. These studies will include the comparison of biochemical and immunological characteristics of FcalphaR and IBFalpha by using SDS-PAGE, immunoblots and isoelectric focusing. We will continue to develop and characterize monoclonal antibodies to FcalphaR and IBFalpha. Biological function of FcalphaR/IBFalpha will be done in B cell cultures. Furthermore, we will produce additional Th cell clones and hybridomas for study of the TCR and FcalphaR. Finally, we will clone the gene(s) which code for FcalphaR and IBFalpha from FcalphaR T cell lines. These studies should provide a molecular basis for IgA isotype-specific immunoregulation.
