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This paper shows that residues of the transmembrane region, located near the luminal side, are critical for Ii to trimerize and assemble with MHC class II.
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This paper shows that the amino-terminal extension of the p35/p43 Ii cytoplasmic tail is phosphorylated at key serine residues in human APC lines and provides evidence that this phosphorylation is critical for direct delivery of these Ii isoforms from the trans-Golgi reticulum to MIIC.
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This paper shows that proteolytic processing of native proteins in lysosomal extracts can be initiated by an asparaginyl endopeptidase.
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Carrasco-Marin E., Paz-Miguel J.E., Lopez-Mato P., Alvarez-Dominguez C., Leyva-Cobian F. Oxidation of defined antigens allows protein unfolding and increases both proteolytic processing and exposes peptide epitopes which are recognized by specific T cells. Immunology. 95:1998;314-321.
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Aichinger G., Karlsson L., Jackson M.R., Vestberg M., Vaughan J.H., Teyton L., Lechler R.I., Peterson P.A. Major histocompatibility complex class II-dependent unfolding, transport, and degradation of endogenous proteins. J Biol Chem. 272:1997;29127-29136.
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Pinet V.M., Long E.O. Peptide loading onto recycling HLA-DR molecules occurs in early endosomes. Eur J Immunol. 28:1998;799-804.
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Vergelli M., Pinet V., Vogt A.B., Kalbus M., Malnati M., Riccio P., Long E.O., Martin R. HLA-DR-restricted presentation of purified myelin basic protein is independent of intracellular processing. Eur J Immunol. 27:1997;941-951.
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Pierre P., Turley S.J., Gatti E., Hull M., Meltzer J., Mirza A., Inaba K., Steinman R.M., Mellman I. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature. 388:1997;787-792.
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17
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This paper shows that in immature murine dendritic cells, grown in granulocyte/macrophage-colony-stimulating factor plus IL-3, lysosomal Ii proteolysis by cathepsin S is blocked by cystatin C. Relief of this inhibition upon maturation allows Ii proteolysis, peptide loading, and export of MHC class II to the cell surface to proceed.
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Pierre P., Mellman I. Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell. 93:1998;1135-1145. This paper shows that in immature murine dendritic cells, grown in granulocyte/macrophage-colony-stimulating factor plus IL-3, lysosomal Ii proteolysis by cathepsin S is blocked by cystatin C. Relief of this inhibition upon maturation allows Ii proteolysis, peptide loading, and export of MHC class II to the cell surface to proceed.
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Pierre, P.1
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This paper shows, using double-knockout mice, that Ii is dispensable for protection of mice against progressive infection with Leishmania major, and that both in the presence and absence of Ii, protection requires H2-M.
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Swier K., Brown D.R., Bird J.J., Martin W.D., Van Kaer L., Reiner S.L. A critical, invariant chain-independent role for H2-M in antigen presentation. J Immunol. 160:1998;540-544. This paper shows, using double-knockout mice, that Ii is dispensable for protection of mice against progressive infection with Leishmania major, and that both in the presence and absence of Ii, protection requires H2-M.
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Invariant chain-independent function of H-2M in the formation of endogenous peptide-major histocompatibility complex class II complexes in vivo
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b-bound endogenous peptides in knockout mice lacking H2-M, Ii, or both. These peptides are presented at almost wild-type levels in the absence of Ii; none are presented in H2-M single knockouts, and varying levels of presentation are seen when both Ii and H2-M are absent.
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b-bound endogenous peptides in knockout mice lacking H2-M, Ii, or both. These peptides are presented at almost wild-type levels in the absence of Ii; none are presented in H2-M single knockouts, and varying levels of presentation are seen when both Ii and H2-M are absent.
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Bikoff E.K., Kenty G., Van Kaer L. Distinct peptide loading pathways for MHC class II molecules associated with alternative Ii chain isoforms. J Immunol. 160:1998;3101-3110.
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The influence of invariant chain on the positive selection of single T cell receptor specificities
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Surh C.D., Lee D.S., Fung-Leung W.P., Karlsson L., Sprent J. Thymic selection by a single MHC/peptide ligand produces a semidiverse repertoire of CD4+ T cells. Immunity. 7:1997;209-219.
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0/0 mice. Immunity. 7:1997;187-195.
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0030805229
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Dendritic cells from mice lacking the invariant chain express high levels of membrane MHC class II molecules in vivo
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Rovere P., Forquet F., Zimmermann V.S., Trucy J., Ricciardi-Castagnoli P., Davoust J. Dendritic cells from mice lacking the invariant chain express high levels of membrane MHC class II molecules in vivo. Adv Exp Med Biol. 417:1997;195-201.
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0030790791
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Functionality of major histocompatibility complex class II molecules in mice doubly deficient for invariant chain and H-2M complexes
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Invariant chain and DM edit self-peptide presentation by major histocompatibility complex (MHC) class II molecules
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Katz J.F., Stebbins C., Appella E., Sant A.J. Invariant chain and DM edit self-peptide presentation by major histocompatibility complex (MHC) class II molecules. J Exp Med. 184:1996;1747-1753.
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0030990387
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In the absence of the invariant chain, HLA-DR molecules display a distinct array of peptides which is influenced by the presence or absence of HLA-DM
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Lightstone L., Hargreaves R., Gabriele B., Peterson M., Aichinger G., Lombardi G., Lechler R. In the absence of the invariant chain, HLA-DR molecules display a distinct array of peptides which is influenced by the presence or absence of HLA-DM. Proc Natl Acad Sci USA. 94:1997;5772-5777.
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The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3
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33
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0032055577
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Identification of a sequence that mediates promiscuous binding of invariant chain to MHC class II allotypes
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Using Ii molecules in which groove-binding and adjacent regions of CLIP were replaced by antigenic peptide or nonsense sequences, this paper and [34] show that Ii residues 81-87 contribute to allele-independent MHC class II binding.
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Siebenkotten I.M., Carstens C., Koch N. Identification of a sequence that mediates promiscuous binding of invariant chain to MHC class II allotypes. J Immunol. 160:1998;3355-3362. Using Ii molecules in which groove-binding and adjacent regions of CLIP were replaced by antigenic peptide or nonsense sequences, this paper and [34] show that Ii residues 81-87 contribute to allele-independent MHC class II binding.
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Siebenkotten, I.M.1
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Stumptner P., Benaroch P. Interaction of MHC class II molecules with the invariant chain: role of the invariant chain (81-90) region. EMBO J. 16:1997;5807-5818.
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An altered invariant chain protein with an antigenic peptide in place of CLIP forms SDS-stable complexes with class II αβ dimers and facilitates highly efficient peptide loading
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Barton G.M., Rudensky A.Y. An altered invariant chain protein with an antigenic peptide in place of CLIP forms SDS-stable complexes with class II αβ dimers and facilitates highly efficient peptide loading. Int Immunol. 10:1998;1159-1165.
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0033082484
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Using amino- and carboxy-terminal truncations of Ii, this paper shows that a region immediately carboxy-terminal to CLIP (residues 103-118) and the trimerization domain cooperate to mediate binding to MHC class II outside the antigen binding groove.
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Thayer W.P., Ignatowicz L., Weber D.A., Jensen P.E. Class II-associated invariant chain peptide-independent binding of invariant chain to class II MHC molecules. J Immunol. 162:1999;1502-1509. Using amino- and carboxy-terminal truncations of Ii, this paper shows that a region immediately carboxy-terminal to CLIP (residues 103-118) and the trimerization domain cooperate to mediate binding to MHC class II outside the antigen binding groove.
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J Immunol
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Thayer, W.P.1
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0033152268
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One of two unstructured domains of Ii becomes ordered in complexes with MHC class II molecules
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This paper shows that except for the trimerization domain, E. coli-derived soluble Ii (72-216) is disordered in solution, as demonstrated by sharp peaks in nuclear magnetic resonance spectra. Residues on either side of the CLIP region become ordered upon binding to DR, resulting in broadening of spectral peaks.
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Jasanoff A., Song S., Dinner A.R., Wagner G., Wiley D.C. One of two unstructured domains of Ii becomes ordered in complexes with MHC class II molecules. Immunity. 761:1999;761-768. This paper shows that except for the trimerization domain, E. coli-derived soluble Ii (72-216) is disordered in solution, as demonstrated by sharp peaks in nuclear magnetic resonance spectra. Residues on either side of the CLIP region become ordered upon binding to DR, resulting in broadening of spectral peaks.
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Immunity
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Jasanoff, A.1
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38
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0032401758
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Structure of a trimeric domain of the MHC class II-associated chaperonin and targeting protein Ii
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This paper uses an ingenious combination of differential isotope labeling of Ii chains and multidimensional nuclear magnetic resonance to determine the structure of the luminal Ii trimerization domain in solution. This domain adopts a novel fold employing numerous interchain contacts to form a roughly cylindrical structure allowing assembly of three MHC class II αβ dimers around its lateral faces.
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Jasanoff A., Wagner G., Wiley D.C. Structure of a trimeric domain of the MHC class II-associated chaperonin and targeting protein Ii. EMBO J. 17:1998;6812-6818. This paper uses an ingenious combination of differential isotope labeling of Ii chains and multidimensional nuclear magnetic resonance to determine the structure of the luminal Ii trimerization domain in solution. This domain adopts a novel fold employing numerous interchain contacts to form a roughly cylindrical structure allowing assembly of three MHC class II αβ dimers around its lateral faces.
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EMBO J
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0039547996
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Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S
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This study shows by X-ray crystallography that the alternatively spliced cathepsin L inhibitor domain in Ii p41 adopts a novel variant of the thyroglobulin domain fold. Inhibitory interactions with cathepsin L are reminiscent of those found for cystatins, but additional contacts not seen for cystatins account for target enzyme specificity.
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Guncar G., Pungercic G., Klemencic I., Turk V., Turk D. Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S. EMBO J. 18:1999;793-803. This study shows by X-ray crystallography that the alternatively spliced cathepsin L inhibitor domain in Ii p41 adopts a novel variant of the thyroglobulin domain fold. Inhibitory interactions with cathepsin L are reminiscent of those found for cystatins, but additional contacts not seen for cystatins account for target enzyme specificity.
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EMBO J
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Guncar, G.1
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MHC class II-associated invariant chain peptide replacement by T cell epitopes: Engineered invariant chain as a vehicle for directed and enhanced MHC class II antigen processing and presentation
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Malcherek G., Wirblich C., Willcox N., Rammensee H-G., Trowsdale J., Melms A. MHC class II-associated invariant chain peptide replacement by T cell epitopes: engineered invariant chain as a vehicle for directed and enhanced MHC class II antigen processing and presentation. Eur J Immunol. 28:1998;1524-1533.
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The CLIP-substituted invariant chain efficiently targets an antigenic peptide to HLA class II pathway in L cells
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Hum Immunol
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0033577804
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+ T cells
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