Author/Editor		Zavašnik-Bergant, Valentina; Kos, Janko
Title		Vloga invariantne verige in cisteinskih proteinaz v antigen predstavitvenih celicah
Translated title		Role of invariant chain and cysteine proteinases in antigen presenting cells
Type		članek
Source		Med Razgl
Vol. and No.		Letnik 39, št. Suppl 4
Publication year		2000
Volume		str. 137-42
Language		slo
Abstract		Activation of CD4+ (helper) T cells is an important step in an adaptive immune response. Antigen-presenting cells are capable of generating antigenic peptides which are bound to major histocompatibility class 2 molecules (MHC 2) and presented subsequently for recognition to CD4+ T cells. Lysosomal proteinases (cathepsins) are required in two convergent processes. First, in antigen-presenting cells they degrade endocitosed antigens into antigenic peptides. Second, they proccess an invariant chain prior to its release from MHC 2 binding site, facilitating loading of antigenic peptides to MHC 2. Cathepsin S plays an essential role in removal of an invariant chain in B cells, macrophages and dendritic cells, whereas cathepsin L apparently does so in thymic epithelial cells. Specific monoclonal and polyclonal antibodies against the human invariant chain, cathepsin S and cathepsin L have been prepared in our laboratory. Using immunohistochemical analysis we detected cathepsin S in subcapsular and trabecular sinuses together with tissue macrophages. Co-localization of an invariant chain with cathepsin S, but not with cathepsin L was confirmed by fluorescent confocal microscopy. Our results are consistent with the hypothesis that cathepsin S participates in degradation of an invariant chain in antigen-presenting cells.
Summary		Aktivacija CD4+-limfocitov T (celic T pomagalk) je pomemben del adaptivnega imunskega odziva. Razgradnja beljakovin (antigenov) in vezava nastalih peptidov na molekule poglavitnega histokompatibilnostnega kompleksa 2. razreda (MHC2), ki sodelujejo pri predstavitvi antigenov CD4+-limfocitom T, poteka v antigen predstavitvenih celicah. Lizosomske proteinaze (katepsini) sodelujejo pri dveh povezanih proteolitskih procesih pri razgradnji antigenov v peptide ter pri razgradnji invariantne verige, kar sprosti vezavno mesto za omenjene peptide na molekuli MHC 2. Glavno vlogo pri proteolitski razgradnji invariantne verige imata katepsin S (v limfocitih B, makrofagih in dendritičnih celicah) in katepsin L (v specializiranih epitelijskih celicah priželjca). Pripravili smo specifična monoklonska in poliklonska protitelesa proti obliki človeške invariantne verige MHC 2 p41 in proti katepsinoma S in L. Z imunohistokemijsko analizo smo določili prisotnost katepsina S v tkivnih makrofagih na področju subkapsularnih in trabekularnih sinusov človeške bezgavke. S konfokalno fluorescenčno mikroskopijo smo opazili solokalizacijo invariantne verige s katepsinom S, ne pa s katepsinom L. Naši rezultati potrjujejo pomembno vlogo katepsina S pri razgradnji invariantne verige v antigen predstavitvenih celicah.
Descriptors		ANTIGEN-PRESENTING CELLS CYSTEINE PROTEINASES LYMPH NODES HISTOCOMPATIBILITY ANTIGENS CLASS II CATHEPSINS ANTIGEN PRESENTATION