Naslov
Heat shock protein gp96: Rare simplicity

Autori
Štrbo, Nataša ; Sotošek Tokmadžić, Vlatka ; Ćupurdija, Kristijan ; Juretić, Koraljka ; Laškarin, Gordana ; Dorčić, Dorotea ; Dupor, Jana ; Randić, Ljiljana ; Podack, Eckhard ; Rukavina, Daniel

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Croatian Immunological Society Annual Meeting : Abstract book / Jonjić, Stipan - Rijeka : Hrvatsko imunološko društvo, 2003, 57-57

Skup
Croatian Immunological Society Annual Meeting

Mjesto i datum
Brijuni, Hrvatska, 17.10.2004. - 19.10.2004

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
heat shock protein; NK cell; T-cell receptor

Sažetak
Heat shock proteins (HSPs) are the most abundant and ubiquitous intracellular chaperons performing a multitude of housekeeping functions (ie. protein folding, facilitation of protein transport). HSPs-peptide complex "shuttle" antigenic peptides into MHC class I presentation pathway of antigen presenting cells (APCs). Recently, specific receptor (CD91) for gp96 has been identified on dendritic cells (DC). Gp96 is a major component of the lumen of the endoplasmatic reticulum. The presence of gp96 in the extracellular milieu acts as an excellent message that alerts the APCs to physical damage of the surrounding cells (bacterial and viral infections or mechanical injury). We have studied the molecular and cellular mechanisms of CTL and NK cell expansion by tumor secreted gp96-Ig as well as expression of gp96 at the materno-fetal interface to clarify the role of gp96 as a molecule responsible for breaking the state of tolerance in tumor immunity and on the implantation site. Ovalbumin specific T-cell receptor (TCR) transgenic CD8+ cells (OT1) were adoptively transferred in syngeneic C57Bl/6 mice. Secreted heat shock protein gp96-Ig was constructed by replacment of endoplasmic reticulum retention signal with Fc portion of IgG1, transfected into EG7 (EG7-gp96-Ig) and used in vivo. OT1 expansion was quantitated with Kb-SIINFEKL tetramer by flow cytometry, ELISPOT. We have examined the localization of the gp96 and its receptor CD91 by immunohistology in decidual tissue from women during the first trimester of normal pregnancy. Decidual cell isolation was accomplished by enzymatic digestion. Immunofluorescency was used to analyze the phenotype of CD91 positive cells. Tumor-secreted gp96-Ig is highly immunogenic and triggers CD8 T cell-mediated tumor rejaction. In vivo secreted gp96-Ig cause NK activation and clonal expansion of specific CD8+ CTLS in wilde type mice and Fas-L deficient mice, but not perforin- (PKO) and IFN-g-deficient mice. In the decidua, highest expression of gp96 was detected on extravillous citotrophoblast cells. The phenotype of decidual CD91+ cells revealed that HLA-DR+, CD83+ and CD56+ cells express the gp96 receptor. The data demonstrate an essential role for perforin mediated functions in the activation of innate and adaptive immunity by gp96-peptide complex. Crosspresentation of antigens by gp96 seems to require a perforin-dependent positive feedback loop between NK cells and DC for both sustained NK activation and clonal CTL expansion. Heterogeneous expression of gp96 (being most intense on extravillous citotrophoblast cells) at the materno-fetal interface, suggests a regulatory role of this stress protein and the ability of gp96 to mediate activation of APCs and CD56+ cells in decidua.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA