Medd, Patrick Goldsmith; (1999) Cellular biology of antigen processing: The role of cathepsin E. Doctoral thesis (Ph.D), UCL (University College London).

Preview

Text Cellular_biology_of_antigen_pr.pdf Download (22MB) | Preview

Abstract

The enzymes responsible for the generation of antigenic peptides for major histocompatibility complex (MHC) class II restricted antigen presentation are poorly characterised. One enzyme proposed to play a role in this process is the aspartic proteinase cathepsin E. To date, there has been no clear demonstration as to whether cathepsin E encounters internalised exogenous antigen within antigen presenting cells, and therefore whether this enzyme can function in MHC class II antigen processing. In this thesis the subcellular localisation of cathepsin E is examined using confocal microscopy and density gradient electrophoresis. In a human B cell line, FC7, cathepsin E distribution was found to be peripheral and diffuse. Cathepsin E was excluded from the later (twenty minutes plus) stages of the endocytic route and the MHC class II containing compartment. In the MHC class II positive melanoma cell line Mel JuSo, cathepsin E showed a different distribution, including a vesicular component not seen in FC7. This vesicular structure did not contain MHC class II, transferrin receptor or CD63 and was not endocytic. Only mature cathepsin E appeared to occupy this vesicular structure. The dendritic cell is the most potent antigen presenting cell yet described. Human monocytes were found not to express cathepsin E, but peripheral blood derived dendritic cells, generated from these monocytes, were strongly positive for this enzyme. Subcellular cathepsin E in these dendritic cells was reticular and mainly peripheral in distribution. The enzyme did not appear to be within fluorochrome traced endosomes, and was again excluded from the MHC class II containing compartment. These results indicate that, in human B cells and peripheral blood derived dendritic cells, endocytic antigen proteolysis by cathepsin E does not play a role in the generation of MHC class II bound antigenic peptides.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as XMLCSVJSON

Downloads by country - last 12 months

Export as JSONCSVXML

Archive Staff Only

View Item