Date

3-2014

Document Type

Thesis

Degree Name

M.S.

Department

Dept. of Molecular Microbiology and Immunology

Institution

Oregon Health & Science University

Abstract

MHCI molecules present antigens to CD8+ lymphocytes from intracellular pathogens. The mechanism by which antigens are processed and presented to classically restricted T cells has been described. However the mechanisms of antigen processing and presentation to non-classically restricted T cells are less well understood. Moreover, the vesicular trafficking molecules involved in antigen presentation and processing on all MHCI molecules are unknown. It was determined that Rab6 is involved in the presentation of Mycobacterium tuberculosis antigens to MR1 restricted T cells from infected epithelial cells and not to classically restricted or HLA-E restricted T cells. Rab6 is involved in exocytosis from the Golgi as well as in retrograde transport from the endosomes to the Golgi and from the Golgi to the Endoplasmic Reticulum (ER). Knockdown of Rab6 using siRNA showed this protein is not involved in surface expression of MR1 in uninfected cells. MR1 translocates to the plasma membrane upon binding the ligand 6-Formyl Pterin (6-FP), causing the overall surface expression of MR1 to increase. Flow cytometry and fluorescence microscopy demonstrated that Rab6 is also not involved in this translocation of MR1 to the cell surface. It was observed that Rab6 and MR1-GFP vesicles do not associate within epithelial cells. This suggests that the role of Rab6 in presenting Mtb antigens to MR1 restricted T cells is not related to vesicular trafficking of MR1 to the cell surface or within the cell. Further studies will analyze the role of Rab6 in trafficking of Mtb antigen to be loaded on MR1.

Identifier

doi:10.6083/M4K64GCD

School

School of Medicine

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