IMMUNOPOTENCY OF A VIRAL PEPTIDE ASSEMBLED ON THE CARBOHYDRATE MOIETIES OF SELF IMMUNOGLOBULINS

The T-cell receptor recognizes peptides bound to the major histocompat ibility complex antigens. Synthetic peptides corresponding to microbia l epitopes can efficiently stimulate the in vitro proliferation of T-c ell hybridoma or in vivo, primed T cells, However, the in vivo immune responses elicited by synthetic peptides are weak because of their sho rt half-life and poor immunogenicity. We previously showed that a gene tically engineered immunoglobulin (Ig-HA), in which the CDR3 region of V-H gene was replaced with a viral peptide recognized by CD4(+) T cel ls, was able to deliver this epitope in the correct frame to antigen-p rocessing cells that efficiently presented the peptide to T cells. Rec ently, we developed an enzymatic method to assemble viral pep tides on the sugar moieties of immunoglobulins without alteration of the biolo gical functions of either molecule, The viral peptide carried by these conjugates was twenty times more efficient In activating a T-cell hyb ridoma than the free peptide as calculated on a molar basis. We show t hat such conjugates are able to prime in vivo the precursors of peptid e-specific T cells and to induce proliferation of naive lymphocytes fr om transgenic mice expressing a peptide-specific T-cell receptor in bo th CD4 and CD8 T-cell subsets, Our results suggest that peptides enzym atically linked to the carbohydrate moieties of immunoglobulins, using galactose residues as peptide acceptor, can be used as a safe and eff icient delivery system of protective epitopes for the prevention of in fectious diseases. The enzymatic engineering of immunoglobulins may al so allow the development of immunotherapeutic agents to deliver antago nist peptides to autoreactive T cells or to direct immunomodulatory ag ents such as interleukins or cytolytic drugs to tumor cells.