טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentCohen Cyrille
SubjectThe Cancer Cell as an Antigen-Presenting Cell: Study of
Anti-Tumor Immunity with Recombinant MHC/peptide
Complexes and T-Cell Receptor-Like
Antibodies
DepartmentDepartment of Biology
Supervisor Professor Yoram Reiter


Abstract

  The MHC/peptide complex holds a pivotal role in the study of anti-tumor and anti-viral cellular immune responses. Therefore, we aimed in this research to develop and use new immunological molecules to study both cytotoxic T-cell immune responses and antigen presentation by tumor/viral infected cells.

 We have produced recombinant scHLA-A2/peptide complexes that were subsequently used for two major experimental strategies: 1) Molecular characterization of CTL-mediated immune responses, using MHC/peptide tetramers and 2) Selection and characterization of recombinant antibodies with TCR-like specificity.

  We were able to show that CD8 is recruited and participates directly in TCR-peptide-MHC interactions before the MHC-peptide complex has stably bound to the TCR. In addition, we were able to study simultaneously binding and activation of T-cells by combining both technologies of single-chain MHC/peptide tetramers and the CellScan.

  For the second approach, we have isolated high affinity recombinant antibodies with TCR-like specificity from a naïve phage library. These antibodies, directed toward the melanoma, breast and viral-associated antigens, were able to recognize the native MHC-peptide complex expressed on the surface of APC as well as tumor or viral-infected cells. We have shown the utility of these unique molecules for several fields of research:

1) For studying antigen MHC-peptide presentation in cancer/viral infected cells.

2) For developing new immunotherapy targeting molecules

3) For studying structure-function relationships in TCR-peptide-MHC interactions.   

4) For elucidating the mechanisms related to viral infection.