The importance of the mucosal immune system in pathogenesis HIV infection and its potential significance in the production of protective vaccines has only recently been acknowledged. It is clear that infection with this virus profoundly affects the mucosal immune system. Particularly noteworthy is the effect on the gastrointestinal tract. The present application proposes to extend ongoing studies aimed at defining parameters of the human IgA system in HIV infection. This will be done by fully characterizing the functions of secretory IgA anti-HIV antibodies isolated from the colostrum of seropositive women, determining the role(s) of IgA antibodies in mediating infection of mucosal epithelial cells and by studying IgA function in vivo using severe combined immunodeficient (SCID) mice reconstituted with human cells and infected with HIV. The following specific aims are proposed: 1. Determination of the potential of IgA antibodies to enhance HIV infection of epithelial cells via either the polymeric immunoglobulin receptor (secretory compontent, SC) or by carbohydrate-mediated interactions (galactose of IgA molecules and cell surface galactosyltransferase), using the HT29 and T84 human cell lines of gastrointestinal origin known to express SC and galactosyltransferase; 2. Elucidation of the role of cytokines in enhancement of infection and uptake of HIV by gastrointestinal epithelial cell lines; 3. Characterization of the function(s) of secretory IgA anti-HIV antibodies isolated from the colostrum of HIV-positive mothers.
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