The long term objective of this project is to regulate antigen uptake by M cells and transport to lymphoid cells in intestinal lymphoid organs. The ability to target M cells with probes adherent to M cells will be investigated in mouse and rabbit animal models. Transport of a mouse monoclonal antibody against the rabbit M cell surface will be compared to a monoclonal antibody that does not bind to M cell surfaces. Since these mouse monoclonal antibodies are also foreign proteins to rabbits, levels of antigen specific IgA in mucosal secretions will be studied to determine whether binding will enhance generation of a mucosal immune response. Lectins which bind to M cells will be used as vectors to enhance antigen uptake by M cells and development of a subsequent IgA immune response. The ability to regulate uptake of particles by M cells will be examined in vivo by using fluorescent microspheres of two different colors conjugated to M cell binding lectins. M cells which have been stimulated by gamma- interferon to express cell surface la will be targeted with anti-la:antigen conjugates. The effect of antigen uptake by M cells on the activation of mucosal T cells will be defined. Activation of T cells will be determined by detection of a T cell activation molecule on mucosal T cells and rabbit T cell lines. The ability of M cells to convey activation signals in vivo will be examined after mitogen binding to M cell surfaces. The capacity of activated T cells to selectively bind to M cells will be assessed in vitro to determine factors involved in infiltration of M cells by lymphocytes. Understanding M cell uptake of antigens and particles is relevant for optimizing oral immunization, combating intestinal infection, and delineating the pathogenesis of mucosal immunologic diseases.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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General Medicine A Subcommittee 2 (GMA)
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Acambis, Inc.
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