Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
TANDEM REPEATS OF T-HELPER EPITOPES ENHANCE IMMUNOGENICITY OF FUSION PROTEINS BY PROMOTING PROCESSING AND PRESENTATION
Autore:
KJERRULF M; LOWENADLER B; SVANHOLM C; LYCKE N;
Indirizzi:
GOTHENBURG UNIV,DEPT MED MICROBIOL & IMMUNOL,GULDHEDSGATAN 10 S-41346GOTHENBURG SWEDEN GOTHENBURG UNIV,DEPT MED MICROBIOL & IMMUNOL S-41346 GOTHENBURG SWEDEN PHARMACIA AB,BIOSCI CTR S-11287 STOCKHOLM SWEDEN
Titolo Testata:
Molecular immunology
fascicolo: 8-9, volume: 34, anno: 1997,
pagine: 599 - 608
SICI:
0161-5890(1997)34:8-9<599:TROTEE>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
B-CELL RESPONSES; ANTIGEN PRESENTATION; LYMPHOCYTES-B; IMMUNOGLOBULIN RECEPTORS; PEPTIDE VACCINES; IA-ANTIGEN; SPECIFICITY; RECOGNITION; ANTIBODIES; PROTEASES;
Keywords:
ANTIGEN PROCESSING; FUSION PROTEIN; TARGETING; T CELL EPITOPE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
43
Recensione:
Indirizzi per estratti:
Citazione:
M. Kjerrulf et al., "TANDEM REPEATS OF T-HELPER EPITOPES ENHANCE IMMUNOGENICITY OF FUSION PROTEINS BY PROMOTING PROCESSING AND PRESENTATION", Molecular immunology, 34(8-9), 1997, pp. 599-608

Abstract

Empirical findings have shown that recombinant chimeric proteins may be made more immunogenic if T helper epitopes are incorporated as tandem repeats. In the present study we investigated the mechanisms responsible for the enhanced immunogenicity of fusion proteins composed of the heat-stable enterotoxin of enterotoxigenic E. coli (STa) linked to multiple copies of the ovalbumin(323-339) T helper epitope (oval and aconnecting dimer of an Ig-binding region of Staphylococcus nta eus protein A (ZZ), which were previously shown to stimulate strong anti-STatitres in mice. We used B cell and macrophage cell lines as APC and IL-2 production by ova-specific T cells as our read-out system. Fusion proteins containing four repeated T helper epitopes were found to be the most immunogenic and resulted in 50-fold higher IL-2 production than constructs with a single T helper epitope. Under limiting APC conditions the construct with four epitopes was the best inducer of IL-2, indicating that this construct was most effectively processed by the APC. Analysis of IL-2R alpha expression by flow cytometry confirmed that four copies gave the highest frequency of activated T cells in culture, indicating a direct correlation between ability to activate T cells and IL-2 production in culture. Also in vivo, the fusion protein with four epitopes exhibited the strongest T cell priming effect. Moreover,both in vitro and in vivo, the ZZ construct was found to serve as an efficient means for targeting of the fusion proteins to B cells, thereby allowing access to the Ig receptor uptake pathway for Ag. The present study provides direct evidence that fusion proteins can be constructed to optimize processing in the individual APC and enhance activation of clonal T cells. (C) 1997 Published by Elsevier Science Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 05:24:11