An investigation of the distribution of antigen fed in tolerogenic or immunogenic forms

It remains unclear which cells present fed antigen and whether their phenotype and/or activation state differs between oral tolerance and priming. Furthermore, it is also controversial whether the presentation occurs locally in the gut and/or systemically. Clarifying these issues will be important for the design and use of oral vaccines, the therapeutic use of oral tolerance and understanding of IBD. Previous studies using activation of T cell receptor transgenic T cells to compare local and systemic distribution of fed antigen have yielded conflicting results. We have therefore employed the C4H3 antibody, specific for HEL peptide (46-61) in the context of I-Ak, to examine antigen distribution in oral tolerance and priming. Our studies indicate that immunologically relevant antigen can be detected in both local and systemic lymphoid tissue soon after feeding antigen in tolerogenic or immunogenic forms. Furthermore, targeting fed antigen to BcR tg B cells via their specific B cell receptor also results in local and systemic presentation and leads to up-regulation of costimulatory molecules on these cells that suggests their role in presentation of the fed antigen.