Mapping functional regions in the lumenal domain of the class II- associated invariant chain

The MHC class II-associated invariant chain interacts in trimeric form with class II molecules, inhibits peptide binding, and mediates targeting of class II molecules to endosomal compartments. To dissect the different functions of the invariant (Ii) chain, a set of cDNAs, encoding truncated forms of the Ii chain, was constructed. mRNAs, transcribed from these cDNAs were translated in vitro, together with mRNAs encoding class II HLA DR1 alpha and beta subunits. An Ii chain truncation that contains the 104 NH2-terminal amino acids was able to associate with class II molecules. This construct contains the region from which class II-associated Ii chain peptides (CLIP, amino acids 81- 104) are derived. The absence of a further eight residues at the COOH terminus results in a construct of 96 amino acids that is unable to associate with class II molecules. Association of the truncated Ii chains with class II molecules showed a strict correlation with inhibition of peptide binding. Removal of the NH2-terminal cytoplasmic tail and transmembrane region of Ii chain and its replacement with a cleavable signal sequence led to aberrant folding and impaired association with class II molecules. The region between amino acids 163 and 183 was found to be essential for visualization of Ii chain homotrimers by covalent cross-linking.

• Publication year

  1994

• Venue

  Journal of Experimental Medicine

• Publication date

  1994-08-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/JEM.180.2.623PMID 7519244PMCID 2191624
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Assembly of HLA DR1 molecules translated in vitro: binding of peptide in the endoplasmic reticulum precludes association with invariant chain.

  1994cited by this paper
• Assembly, transport, and function of MHC class II molecules.

  1994cited by this paper
• Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles

  1993cited by this paper
• The segment of invariant chain that is critical for association with major histocompatibility complex class II molecules contains the sequence of a peptide eluted from class II polypeptides.

  1993influential reference
• Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size

  1992cited by this paper
• Invariant chain can function as a chaperone protein for class II major histocompatibility complex molecules.

  1992cited by this paper
• Assembly and transport properties of invariant chain trimers and HLA-DR-invariant chain complexes.

  1992cited by this paper
• Peptides presented to the immune system by the murine class II major histocompatibility complex molecule I-Ad.

  1992cited by this paper
• Invariant chain--a regulator of antigen presentation.

  1992cited by this paper
• HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells

  1992cited by this paper
• HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides

  1992cited by this paper
• Chemistry and functional role of the invariant chain.

  1992cited by this paper
• Sequence analysis of peptides bound to MHC class II molecules

  1991cited by this paper
• Formation of a nine-subunit complex by HLA class II glycoproteins and the invariant chain

  1991cited by this paper
• Proteolysis of the class II-associated invariant chain generates a peptide binding site in intracellular HLA-DR molecules.

  1991cited by this paper
• Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments

  1991cited by this paper
• Invariant chain promotes egress of poorly expressed, haplotype-mismatched class II major histocompatibility complex A alpha A beta dimers from the endoplasmic reticulum/cis-Golgi compartment.

  1991cited by this paper
• MHC class II-associated invariant chain contains a sorting signal for endosomal compartments.

  1990cited by this paper
• Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding

  1990cited by this paper
• Intracellular transport of class II MHC molecules directed by invariant chain

  1990influential reference
• Invariant chain distinguishes between the exogenous and endogenous antigen presentation pathways

  1990cited by this paper
• The biosynthetic pathway of MHC class II but not class I molecules intersects the endocytic route.

  1990cited by this paper
• Human major histocompatibility complex class II invariant chain is expressed on the cell surface.

  1990cited by this paper
• Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens

  1990influential reference
• Structural model of HLA-DR1 restricted T cell antigen recognition.

  1988cited by this paper
• Alternative splicing and alternative initiation of translation explain the four forms of the Ia antigen‐associated invariant chain.

  1986cited by this paper
• DNA sequence and characterization of human class II major histocompatibility complex beta chains from the DR1 haplotype.

  1985cited by this paper
• Intracellular class II HLA antigens are accessible to transferrin-neuraminidase conjugates internalized by receptor-mediated endocytosis.

  1985cited by this paper
• Specificity of monoclonal antibodies directed against human and murine class II histocompatibility antigens as analyzed by binding to HLA-deletion mutant cell lines.

  1985cited by this paper
• A human Ia cytoplasmic determinant located on multiple forms of invariant chain (gamma, gamma 2, gamma 3).

  1984cited by this paper
• cDNA clone for the human invariant gamma chain of class II histocompatibility antigens and its implications for the protein structure.

  1983cited by this paper
• Biosynthesis and glycosylation of the invariant chain associated with HLA-DR antigens.

  1982cited by this paper
• Membrane insertion and oligomeric assembly of HLA-DR histocompatibility antigens.

  1982cited by this paper
• Alpha chain of HLA-DR transplantation antigens is a member of the same protein superfamily as the immunoglobulins.

  1982cited by this paper
• Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4

  1970cited by this paper
• DNA sequence and characterization of human class II major histocompatibility complex 8 chains from the DRI haplotype

  year unknowncited by this paper

• CD74 and Proteases: Impact of Location on Immune and Cellular Functions

  2025cites this paper
• Structural insights into human MHC-II association with invariant chain

  2024cites this paper
• CD74 Interacts with Proteins of Enterovirus D68 To Inhibit Virus Replication

  2023cites this paper
• The role of CD74 in cardiovascular disease

  2023cites this paper
• The transmembrane domain and luminal C-terminal region independently support invariant chain trimerization and assembly with MHCII into nonamers

  2021influential citation
• Role of membrane environment and membrane-spanning protein regions in assembly and function of the Class II Major Histocompatibility complex.

  2019cites this paper
• Immune stimulation of rainbow trout reveals divergent regulation of MH class II-associated invariant chain isoforms

  2019cites this paper
• On the structure-function of MHC class II molecules and how single amino acid polymorphisms could alter intracellular trafficking.

  2019cites this paper
• Development of a Molecular Adjuvant to Enhance Antigen-Specific CD8+ T Cell Responses

  2018cites this paper
• The multifaceted roles of the invariant chain CD74--More than just a chaperone.

  2016cites this paper
• Processing of CD74 by the intramembrane protease SPPL2a in B cells : Impact on endosomal trafficking and signaling

  2015cites this paper
• The human‐specific invariant chain isoform Iip35 modulates Iip33 trafficking and function

  2014cites this paper
• The D-6 Mouse Monoclonal Antibody Recognizes the CD74 Cytoplasmic Tail

  2014cites this paper
• During Biosynthesis Virus Superantigen with MHC Class II Association of Mouse Mammary Tumor

  2013cites this paper
• Site Other Than the Peptide Binding Groove Invariant Chain Can Bind MHC Class II at a

  2013cites this paper
• MHC class II antigen presentation by dendritic cells regulated through endosomal sorting.

  2013cites this paper
• Isotype-Specific Chaperone Requirements DM Loss in k Haplotype Mice Reveals

  2013cites this paper
• The p 35 human invariant chain in transgenic mice restores mature B cells in the absence of endogenous CD 74

  2012cites this paper
• Shark class II invariant chain reveals ancient conserved relationships with cathepsins and MHC class II.

  2012cites this paper
• Zelluläre Transport- und Endozytosemechanismen des Zytokins MIF und seiner Rezeptoren

  2012cites this paper
• The p35 human invariant chain in transgenic mice restores mature B cells in the absence of endogenous CD74.

  2012cites this paper
• CD74: an emerging opportunity as a therapeutic target in cancer and autoimmune disease

  2011cites this paper
• Evidence for role of transmembrane helix-helix interactions in the assembly of the Class II major histocompatibility complex.

  2010cites this paper
• Open Access RESEARCH

  2010cites this paper
• FCRN MEDIATED MUCOSAL IMMUNITY AND SUBUNIT VACCINE DELIVERY

  2009cites this paper
• Investigating helix-helix interactions in the transmembrane domains of membrane proteins

  2009cites this paper
• MHC II and the Endocytic Pathway: Regulation by Invariant Chain

  2009cites this paper
• The MHC Class II-Associated Invariant Chain Interacts with the Neonatal Fcγ Receptor and Modulates Its Trafficking to Endosomal/Lysosomal Compartments1

  2008cites this paper
• Endosomal / Lysosomal Compartments Receptor and Modulates Its Trafficking to γ Chain Interacts with the Neonatal Fc The MHC Class II-Associated Invariant

  2008cites this paper
• Peptide binding characteristics of the coeliac disease-associated DQ(α1*0501, β1*0201) molecule

  2007cites this paper
• Protein kinase C delta stimulates antigen presentation by Class II MHC in murine dendritic cells.

  2007cites this paper
• Regulation of MH Class II Associated Invariant Chain in Oncorhynchus mykiss

  2007cites this paper
• The chondroitin sulfate form of invariant chain trimerizes with conventional invariant chain and these complexes are rapidly transported from the trans-Golgi network to the cell surface.

  2007cites this paper
• Sea bass (Dicentrarchus labrax) invariant chain and class II major histocompatibility complex: sequencing and structural analysis using 3D homology modelling.

  2007cites this paper
• Invariant chain transmembrane domain trimerization: a step in MHC class II assembly.

  2006cites this paper
• Class II MHC function in macrophages and mice infected with mycobacterium

  2006cites this paper
• Invariant chain and internalization of mature MHC class II from the cell surface

  2005cites this paper
• Antibodies generated by a novel DNA vaccination identify the MHC class III encoded BAT2 polypeptide.

  2005cites this paper
• Endoplasmic Reticulum-Associated Degradation-Induced Dissociation of Class II Invariant Chain Complexes Containing a Glycosylation-Deficient Form of p411

  2004cites this paper
• DM Loss in k Haplotype Mice Reveals Isotype-Specific Chaperone Requirements 1

  2003cites this paper
• Tab2 is a novel conserved RNA binding protein required for translation of the chloroplast psaB mRNA

  2003cites this paper
• Crystal structure of MHC class II I-Ab in complex with a human CLIP peptide: prediction of an I-Ab peptide-binding motif.

  2003cites this paper
• Asparagine endopeptidase can initiate the removal of the MHC class II invariant chain chaperone.

  2003cites this paper
• Detection of Low-Avidity CD4+ T Cells Using Recombinant Artificial APC: Following the Antiovalbumin Immune Response1

  2003influential citation
• A structure for the trimeric MHC class II-associated invariant chain transmembrane domain.

  2002cites this paper
• Uncoating ATPase Hsc70 is recruited by invariant chain and controls the size of endocytic compartments

  2002cites this paper
• Analysis of two acidic P6 pocket residues in the pH dependency of peptide binding by I-E(k).

  2002cites this paper
• Multiple roles of the invariant chain in MHC class II function.

  2002cites this paper
• Antiovalbumin Immune Response Recombinant Artificial APC : Following the T Cells Using + Detection of Low-Avidity CD 4

  2002influential citation
• Introducing endogenous antigens into the major histocompatibility complex (MHC) class II presentation pathway. Both Ii mediated inhibition and enhancement of endogenous peptide/MHC class II presentation require the same Ii domains

  2001cites this paper
• Glycosylation Signals That Separate the Trimerization from the MHC Class II-binding Domain Control Intracellular Degradation of Invariant Chain*

  2001cites this paper
• Specific treatment of autoimmunity with recombinant invariant chains in which CLIP is replaced by self-epitopes

  2001cites this paper
• Mutation of the invariant chain transmembrane region inhibits II degradation, prolongs association with MHC class II, and selectively disrupts antigen presentation.

  2001cites this paper
• Association of Mouse Mammary Tumor Virus Superantigen with MHC Class II During Biosynthesis1

  2001cites this paper
• MHC Class II Allosteric Site Drugs: New Immunotherapeutics for Malignant, Infectious and Autoimmune Diseases *

  2001cites this paper
• The transmembrane segment of invariant chain mediates binding to MHC class II molecules in a CLIP‐independent manner

  2001cites this paper
• The MHC class II-associated chicken invariant chain shares functional properties with its mammalian homologs.

  2000cites this paper
• Cathepsin S Controls the Trafficking and Maturation of Mhc Class II Molecules in Dendritic Cells

  1999cites this paper
• Chain to Class II MHC molecules Peptide-Independent Binding of Invariant Class II-Associated Invariant Chain

  1999cites this paper
• The Leucine-based Sorting Motifs in the Cytoplasmic Domain of the Invariant Chain Are Recognized by the Clathrin Adaptors AP1 and AP2 and their Medium Chains*

  1999cites this paper
• One of two unstructured domains of Ii becomes ordered in complexes with MHC class II molecules.

  1999cites this paper
• Class II-associated invariant chain peptide-independent binding of invariant chain to class II MHC molecules.

  1999cites this paper
• II-Associated Invariant Chain the Trimerization of the MHC Class A Role for the Transmembrane Domain in

  1999cites this paper
• A role for the transmembrane domain in the trimerization of the MHC class II-associated invariant chain.

  1999cites this paper
• Intracellular transport and peptide loading of MHC class II molecules: regulation by chaperones and motors

  1999cites this paper
• Intracellular traffic to compartments for MHC class II peptide loading: signals for endosomal and polarized sorting

  1999cites this paper
• Deviant trafficking of I‐Ad mutant molecules is reflected in their peptide binding properties

  1999cites this paper
• HLA-DM and the MHC class II antigen presentation pathway

  1999cites this paper
• BALB/c invariant chain mutant mice display relatively efficient maturation of CD4+ T cells in the periphery and secondary proliferative responses elicited upon peptide challenge.

  1999cites this paper
• A Secreted Form of the Major Histocompatibility Complex Class II-associated Invariant Chain Inhibiting T Cell Activation*

  1999cites this paper
• Peptide exchange in MHC molecules

  1999cites this paper
• Peptide loading in the endoplasmic reticulum accelerates trafficking of peptide:MHC class II complexes in B cells.

  1999influential citation
• Peptide Loading in the Endoplasmic Reticulum Accelerates Trafficking of Peptide:MHC Class II Complexes in B Cells

  1999cites this paper
• Class II Allotypes Promiscuous Binding of Invariant Chain to MHC Identification of a Sequence That Mediates

  1998cites this paper
• Endosomal proteolysis and MHC class II function.

  1998cites this paper
• This information is current as Molecules Endocytic Antigen Capture by MHC Class II Large Protein Fragments as Substrates for

  1998cites this paper
• Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation.

  1998cites this paper
• Identification of a sequence that mediates promiscuous binding of invariant chain to MHC class II allotypes.

  1998cites this paper
• 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

  1998cites this paper
• Chain Isoforms Class II Molecules Associated with Alternative Ii Distinct Peptide Loading Pathways for MHC

  1998cites this paper
• A role for HLA‐DO as a co‐chaperone of HLA‐DM in peptide loading of MHC class II molecules

  1998cites this paper
• Intracellular transport of molecules engaged in the presentation of exogenous antigens.

  1998cites this paper
• Cathepsin S activity regulates antigen presentation and immunity.

  1998cites this paper
• Large protein fragments as substrates for endocytic antigen capture by MHC class II molecules.

  1998cites this paper
• T cell recognition of flanking residues of murine invariant chain-derived CLIP peptide bound to MHC class II.

  1998cites this paper
• Structure of a trimeric domain of the MHC class II‐associated chaperonin and targeting protein Ii

  1998cites this paper
• Distinct peptide loading pathways for MHC class II molecules associated with alternative Ii chain isoforms.

  1998cites this paper
• Invariant chain can bind MHC class II at a site other than the peptide binding groove.

  1998cites this paper
• Emerging roles for cysteine proteases in human biology.

  1997cites this paper
• Peptide binding and antigen presentation by class II histocompatibility glycoproteins.

  1997cites this paper
• In Vitro Translation and Assembly of a Complete T Cell Receptor–CD3 Complex

  1997cites this paper
• A new triple-stranded alpha-helical bundle in solution: the assembling of the cytosolic tail of MHC-associated invariant chain.

  1997cites this paper
• HLA-DM acts as a molecular chaperone and rescues empty HLA-DR molecules at lysosomal pH.

  1997cites this paper
• Unique peptide binding characteristics of the disease-associated DQ(alpha 1*0501, beta 1*0201) vs the non-disease-associated DQ(alpha 1*0201, beta 1*0202) molecule.

  1997cites this paper
• Degradation of Mouse Invariant Chain: Roles of Cathepsins S and D and the Influence of Major Histocompatibility Complex Polymorphism

  1997cites this paper
• Selective Modulation of the Major Histocompatibility Complex Class II Antigen Presentation Pathway following B Cell Receptor Ligation and Protein Kinase C Activation*

  1997cites this paper
• Monoclonal antibodies that distinguish between free and complexed heterotrimeric G protein β subunits

  1997cites this paper
• Exon 6 Is Essential for Invariant Chain Trimerization and Induction of Large Endosomal Structures*

  1997cites this paper
• Antigen presentation by MHC class II molecules

  1997cites this paper
• In vivo functions mediated by the p41 isoform of the MHC class II-associated invariant chain.

  1997cites this paper