Immunopotency of a viral peptide assembled on the carbohydrate moieties of self immunoglobulins.
The T-cell receptor recognizes peptides bound to the major histocompatibility complex antigens. Synthetic peptides corresponding to microbial epitopes can efficiently stimulate the in vitro proliferation of T-cell hybridoma or in vivo primed T cells. However, the in vivo immune responses elicited by synthetic peptides are weak because of their short half-life and poor immunogenicity. We previously showed that a genetically engineered immunoglobulin (Ig-HA), in which the CDR3 region of VH gene was replaced with a viral peptide recognized by CD4+ T cells, was able to deliver this epitope in the correct frame to antigen-processing cells that efficiently presented the peptide to T cells. Recently, we developed an enzymatic method to assemble viral peptides on the sugar moieties of immunoglobulins without alteration of the biological functions of either molecule. The viral peptide carried by these conjugates was twenty times more efficient in activating a T-cell hybridoma than the free peptide as calculated on a molar basis. We show that such conjugates are able to prime in vivo the precursors of peptide-specific T cells and to induce proliferation of naive lymphocytes from transgenic mice expressing a peptide-specific T-cell receptor in both CD4 and CD8 T-cell subsets. Our results suggest that peptides enzymatically linked to the carbohydrate moieties of immunoglobulins, using galactose residues as peptide acceptor, can be used as a safe and efficient delivery system of protective epitopes for the prevention of infectious diseases. The enzymatic engineering of immunoglobulins may also allow the development of immunotherapeutic agents to deliver antagonist peptides to autoreactive T cells or to direct immunomodulatory agents such as interleukins or cytolytic drugs to tumor cells.
Brumeanu
T D
TD
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Casares
S
S
Harris
P E
PE
Dehazya
P
P
Wolf
I
I
von Boehmer
H
H
Bona
C A
CA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002241:Carbohydrates / Q000737:chemistry*; D002460:Cell Line; D007136:Immunoglobulins / Q000737:chemistry* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*
D002241:Carbohydrates; D007136:Immunoglobulins; D010455:Peptides; D014764:Viral Proteins