טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentZahavi Efrat
SubjectIsolation and characterization of T-cell Receptor-like
Antibodies Targeting CDl Molecules
DepartmentDepartment of Biology
Supervisors Professor Yehuda Assaraf
Professor Yoram Reiter


Abstract

CD1 molecules are a family of MHC class I like molecules involved in the presentation of lipid antigens to T cells.

Humans express four different CD1 genes: CD1a, CD1b and CD1c make up the group I CD1 molecules, and CD1d belongs to group II CD1 molecules.

The glycolipid a-GalCer, presented by CD1d molecule, was originally isolated from the marine sponge.

α-GalCer has proven to be effective against a broad spectrum of tumors.

Mycobacterium tuberculosis is a human pathogen of enormous importance to global public health. CD1b/GMM complexes (GMM=tuberculosis derived glycolipid) were shown to be presented to the immune system.

Antibodies that are able to recognize CD1-glycolipid complexes, with the same specificity as the T-cell receptor, would be valuable reagents for studying antigen presentation by cancer cells or tubercolosis infected cells.

Therefore, we developed in our laboratory a process to identify and isolate unique antibodies, termed T-Cell Receptor-like antibodies, which recognize and bind to MHC-peptide complexes.

In this work, we were able to isolate recombinant antibodies that exhibit TCR-like binding specific to the CD1d/aGalCer glycolipid. Since the identity of the glycolipids presented by CD1d molecules remains unknown, such antibodies can be used to determine what is the natural epitope that is recognized by NKT cells with specificity to CD1d/aGalCer.

To isolate TCR-like antibodies directed towards CD1b/GMM glycolipid, we used a similar approach.

Several antibodies were isolated. The antibodies did not bind specifically to CD1b/GMM. However, also did not recognize other antigen presenting molecules such as CD1d or MHC class I molecules.