title: Inhibitory p41 isoform of invariant chain and its potential target enzymes cathepsins L and H in distinct populations of macrophages in human lymph nodes.
abstract: Activation of the CD4(+) T-cell mediated immune response relies on the proteolytic capacity of enzymes involved in modulating major histocompatibility complex (MHC) II-associated antigen presentation in antigen-presenting cells (APC). The MHC II-associated chaperone molecule p41 isoform of invariant chain (inhibitory p41 Ii) has been suggested to regulate stability and activity of cathepsin L in these APC. In the present study the human lymph node distribution of non-inhibitory p31 Ii and inhibitory p41 Ii have been compared by differential labelling, using two specific monoclonal antibodies. The distribution of p41 Ii, but not p31 Ii, matched the distribution of cathepsins L and H in subcapsular and cortical sinuses and germinal centres. Co-localization of p41 Ii with cathepsin H was confirmed in strongly CD68(+) sinus-lining macrophages, acting as APC. Furthermore, p41 Ii was determined together with cathepsins L and H in tingible body macrophages, highly phagocytic, but not antigen-presenting cells inside germinal centres. With respect to the physiological function that these two populations of macrophages have in human lymph nodes, our results support a regulatory function of p41 Ii towards cathepsins L and H in human macrophages, associated with the processes of phagocytosis rather than antigen presentation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Ljubljana, Slovenia. tina.zavasnik@ijs.si
authors.forename: Valentina
authors.initials: V
authors.lastname: Zavasnik-Bergant
authors.forename: Ana
authors.initials: A
authors.lastname: Schweiger
authors.forename: Tadeja
authors.initials: T
authors.lastname: Bevec
authors.forename: Rastko
authors.initials: R
authors.lastname: Golouh
authors.forename: Vito
authors.initials: V
authors.lastname: Turk
authors.forename: Janko
authors.initials: J
authors.lastname: Kos
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis*; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008198:Lymph Nodes / Q000737:chemistry*; D008264:Macrophages / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D020033:Protein Isoforms / Q000032:analysis*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D020033:Protein Isoforms; D011994:Recombinant Proteins; C045084:invariant chain; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C534126:CTSH protein, human; D056655:Cathepsin H; C534127:Ctsh protein, mouse