Branched Polypeptides as Antigens for Influenza Virus Hemagglutinin and T-Cell Receptor Subunits
The multiple antigenic peptide (MAP) method was applied to improve the immunogenicity of synthetic peptides representing distinct regions of the influenza virus hemagglutinin (HA). A tetrameric MAP with multiply incorporated overlapping B-and T-cell epitopes was combined with a particular HA sequenc...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
1993
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| Sorozat: | PEPTIDE RESEARCH
6 No. 5 |
| Tárgyszavak: | |
| mtmt: | 1004098 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/32174 |
| Tartalmi kivonat: | The multiple antigenic peptide (MAP) method was applied to improve the immunogenicity of synthetic peptides representing distinct regions of the influenza virus hemagglutinin (HA). A tetrameric MAP with multiply incorporated overlapping B-and T-cell epitopes was combined with a particular HA sequence representing the slightly modified fusion peptide on the C-terminus of the Lys core (MAP-1). As a result of repeated injections of BALB/c mice with MAP-1 but not with the monomeric HA1C[Arg] peptide, the appearance of MAP-1-specific antibodies crossreactive with the acid-pretreated virus could be observed. In vitro studies revealed the potency of the MAP-1 structure to induce proliferation of HA1C[Arg]-primed T-cells, and in vivo studies demonstrated the protective feature of the immune response elicited by MAP-1 and to a lesser extent by the monomeric HA1C[Arg]. The increased level of MAP-1-specific antibodies upon viral challenge shows the activation of MAP-1-specific B- and/or T-cells. The advantage of the previously verified FP3 helper T-cell epitope included in MAP-1 was further utilized to synthesize chimeric structures comprising short fragments of the zeta (MAP-2) or 8 (MAP-3) subunits of the T-cell antigen receptor (TCR) complex. The selected peptides of the zeta- and delta-chain regions failed to elicit an antibody response in BALB/c mice as tetra- or octamers, but the inclusion of the modified fusion region resulted in an immunogenic construction. The chimeric MAP-2 and MAP-3 were successfully used to develop polyclonal and monoclonal antibodies recognizing the corresponding multimeric peptides, but they were unable to bind to the cell membrane-expressed form of the subunits. The MAP constructions that were designed, including appropriately selected B- and helper T-cell epitopes, were proven to be immunogenic; but the crossreactivity of the induced antibodies with the corresponding native proteins was highly dependent on the individual characteristics of the resultant combinations. |
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| Terjedelem/Fizikai jellemzők: | 272-280 |
| ISSN: | 1040-5704 |