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Identifier

000376429

Title

The dual role of invariant chain: HLA- DR transporter and MIF receptor

Alternative Title

Ο διττός ρόλος της σταθερής αλυσίδας: μεταφορέας του HLA- DR και υποδοχέας του MIF

Author

Γεωργούλη, Μαριγούλα- Μιρέλλα

Thesis advisor

Αθανασάκη, Ειρήνη

Reviewer

Γραβανή Α.
Οικονόμου Τ.

Abstract

Invariant chain (Ii) or CD74 is a non-polymorphic glycoprotein whose initial role in antigen presentation was recognized two decades ago. Apart from its role as a chaperone dedicated to MHC-II molecules, CD74 is known to be a high-affinity receptor for Macrophage Migration Inhibitory (MIF).The aim of the present study was to define the roles of CD74 and MIF in the immune surveillance escape process. To this direction, the leukemia cell lines HL-60, Raji, K562 as well as primary pre-B leukemic cells were used, whereas HeLa cells, lacking MHC-II molecules and Ii, were used as control cells. In order to clarify MIF’s involvement in the endosomal pathway, we examined the secretion profile of MIF. Flow cytometry analysis was used to define expression of HLA-DR, CD74, HLA-DM, HLA-DO and MIF in HL-60, Raji, K562, HeLa and primary leukemic cells. Isolated mRNAs were submitted to RT-PCR experiments using CD74 specific primers. Regulation of CD74 and MIF expression by IFN-γ, used as inducer, was tested in K562 and HL-60 cell lines by flow cytometry analysis. The secretion of MIF in a free or exosome-engaged form was evaluated by Elisa experiments. Flow cytometry analysis detected high levels of expression of MIF and CD74 at the cell membrane of all leukemic cells tested, whereas IFN-γ increased MIF expression and induced secretion of MIF in exosome-engaged forms. The unexpected expression of MIF in leukemia cells and the detection of CD74 both intracellularly and membrane bound provides a novel mechanism for escape from immune surveillance. CD74 seemed to possess a key-role in this pathway and react with MIF synergistically. Future studies determining the precise role of the CD74-MIF complex will allow understanding the involvement of MIF in the antigen presentation process.

Language

Greek

Subject

Immune surveillance

Leukemic cells

Διαφυγή ανοσοεπιτήρησης

Λευχαιμικά κύτταρα

Issue date

2012-11-16

Collection

School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses

Type of Work--Post-graduate theses

Views

299

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