UBC Theses and Dissertations
Cross presentation of oral antigens for induction of CD8⁺ T cell responses Chavez Steenbock, Ana Luisa
The biggest challenge of intestinal immunity is inducing tolerance towards harmless antigens derived from food and commensal bacteria while maintaining protection against dangerous pathogens. The dendritic cells (DCs) found in the intestine are crucial to maintaining intestinal homeostasis. DCs are constantly sampling antigens, such as food antigens, found in the intestine and present them to CD8⁺ T cells, which are generally known for killing infected cells. CD8⁺ T cells have been shown to be involved in pathogenesis of some cases of inflammatory bowel disease. Little is known about how these T cells respond towards the presentation of oral antigens derived from food. Therefore, it is important to understand the mechanisms involved in preventing the induction of harmful CD8⁺ T cell responses towards food derived antigens. For this purpose, CD8⁺ T cells with a transgenic T cell receptor that recognizes the food derived antigen ovalbumin were analyzed. It was demonstrated that ovalbumin given to mice orally induced CD8⁺ T cell activation and proliferation. Although the responding CD8⁺ T cells lacked cytolytic activity, they were induced to produce IFN-γ. This observed CD8⁺ T cell activation and proliferation is known to require cross presentation of oral antigens by DCs. Two cross presentation deficient mouse models, ΔYKb and CD74-/-, were used to assess mechanisms in the cross presentation pathway of oral antigens. The ΔYKb mice have a mutated endocytosis motif on MHC-I required for cross presentation and CD74-/- mice lack the CD74 chaperone protein. A low dose of oral ovalbumin resulted in reduced antigen specific CD8⁺ T cell proliferation and activation in the ΔYKb mouse strain only. Given the importance of the endocytosis motif for efficient cross presentation of oral antigens, human MHC-I alleles were examined for possible polymorphism in this motif. All analyzed human MHC-I alleles were conserved in the endocytosis motif. Collectively, this thesis demonstrates that cross presentation is an important pathway for antigen presentation and required for induction of CD8⁺ T cells activation and proliferation towards oral antigens. This mechanism might contribute to intestinal homeostasis and oral tolerance.
Item Citations and Data
Attribution-ShareAlike 3.0 Unported