|Ph.D Student||Cohen Cyrille|
|Subject||The Cancer Cell as an Antigen-Presenting Cell: Study of|
Anti-Tumor Immunity with Recombinant MHC/peptide
Complexes and T-Cell Receptor-Like
|Department||Department of Biology||Supervisor||Professor Yoram Reiter|
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.