Year of Award

2013

Document Type

Dissertation

Degree Type

Doctor of Philosophy (PhD)

Other Degree Name/Area of Focus

Microbiology, Integrative Microbiology and Biochemistry

Department or School/College

Division of Biological Sciences

Committee Chair

Bill Granath

Commitee Members

Scott Wetzel, Jesse Hay, Kevin Roberts, Dave Shepherd, Mike Minnick

Keywords

T cells, trogocytosis, CD4, imaging

Abstract

Antigen recognition by CD4+ T cells leads to large-scale spatial and temporal molecular redistributions, forming the immunological synapse. We have previously shown that upon dissociation, T cells capture large membrane fragments from antigen-presenting cells directly from the immunological synapse. The mechanism and biological significance of this process, termed trogocytosis, is still unclear. In this thesis I examined the impact that trogocytosis has on the individual T cell after capturing molecules from the antigen presenting cell. I employed murine fibroblast cell lines expressing an I-Ek molecule loaded with a covalently attached antigenic peptide (moth cytochrome C 88-103) and with or without a GFP-tagged cytoplasmic tail as antigen presenting cells for T cells from a peptide-specific TCR transgenic mouse. Using a combination of high-resolution microscopy and flow cytometry, In this thesis I showed that the trogocytosed material is retained on the surface of the T cell and is associated with sustained signaling after removal of the antigen presenting cells. The intercellular trogocytosis correlates with alterations in and is associated with sustained survival of the trogocytosis-positive (trog+) cells in vitro. I also showed that sustained signaling in trog+ T cells occurs at the trogocytosed spot and is initiated by the trogocytosed material. I conclude, that after trogocytosis, trog+ T cells present antigen and induce activation of antigen-specific naïve T cells. The findings from this thesis will help to elucidate the role of trogocytosis on CD4+ T cells.

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© Copyright 2013 Douglas Grant Osborne