Self and foreign 60-kilodalton heat shock protein T cell epitope peptides serve as immunogenic carriers for a T cell-independent sugar antigen.
Healthy individuals manifest natural T cell reactivity to epitopes of the 60-kDa heat shock protein (hsp60) of both self and bacterial origin. The present studies were done to learn whether defined peptides of hsp60 could function as T cell carrier epitopes for a poorly immunogenic T-independent capsular polysaccharide, the Vi Ag of Salmonella typhi. Homologous peptides were synthesized from the mouse self-hsp60 molecule (CP1m), from the closely related human hsp60 molecule (CP1h), and from the more distant Escherichia coli (CP1ec) and mycobacterial (CP1mt) hsp60 molecules. The peptides were conjugated to Vi and tested for their immunogenicity in BALB/c (H-2d) and H-2 congenic mice (H-2k and H-2b). We now report that the self-CP1m and cross-reactive CP1h peptides were as immunogenic as was the non-cross-reactive foreign CP1ec peptide. Small amounts of the CP1 peptide, even in PBS, sufficed to induce anti-Vi Abs of the IgG1 (T-dependent) isotype in naive mice. The carrier effect was associated with the ability of the peptides to bind to APC and to induce T cell proliferation. H-2d and H-2k mice, but not H-2b mice responded to CP1m/h and CP1ec. None of the mice responded to CP1mt. No signs of inflammation or autoimmune disease were detected. Thus, natural T cell autoimmunity exists and can be harnessed to provide T cell help for Ab production to a foreign bacterial molecule in a synthetic vaccine.
Könen-Waisman
S
S
Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Fridkin
M
M
Cohen
I R
IR
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000955:Antigens, T-Independent / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011135:Polysaccharides, Bacterial / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014436:Typhoid-Paratyphoid Vaccines / Q000276:immunology
D000907:Antibodies, Bacterial; D000955:Antigens, T-Independent; D002352:Carrier Proteins; D018834:Chaperonin 60; D000939:Epitopes; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D014436:Typhoid-Paratyphoid Vaccines