The CLIP region of invariant chain plays a critical role in regulating major histocompatibility complex class II folding, transport, and peptide occupancy

doi:10.1084/jem.180.3.1107

This Article

	Full Text (PDF, 846K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Romagnoli, P.
	Articles by Germain, R. N.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Romagnoli, P.
	Articles by Germain, R. N.


Social Bookmarking

	What's this?

ARTICLES

The CLIP region of invariant chain plays a critical role in regulating major histocompatibility complex class II folding, transport, and peptide occupancy

P Romagnoli and RN Germain
Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.

Invariant chain (Ii) contributes in a number of distinct ways to the proper functioning of major histocompatibility complex (MHC) class II molecules. These include promoting effective association and folding of newly synthesized MHC class II alpha and beta subunits, increasing transit of assembled heterodimers out of the endoplasmic reticulum (ER), inhibiting class II peptide binding, and facilitating class II movement to or accumulation in endosomes/lysosomes. Although the cytoplasmic tail of Ii makes a key contribution to the endocytic localization of class II, the relationship between the structure of Ii and its other diverse functions remains unknown. We show here that two thirds of the lumenal segment of Ii can be eliminated without affecting its contributions to the secretory pathway events of class II folding, ER to Golgi transport, or inhibition of peptide binding. These same experiments reveal that a short (25 residue) contiguous internal segment of Ii (the CLIP region), frequently found associated with purified MHC class II molecules, is critical for all three functions. Together with other recent findings, these results raise the possibility that the contributions of Ii to the early postsynthetic behavior of class II may depend on its interaction with the class II binding site. This would be consistent with the intracellular behavior of unoccupied MHC class I and class II molecules as incompletely folded proteins and imply a related structural basis for the similar contributions of Ii to class II and of short peptides to class I assembly and transport.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Neumann, J., Koch, N. (2006). A novel domain on HLA-DR{beta} chain regulates the chaperone role of the invariant chain. J. Cell Sci. 119: 4207-4214 [Abstract] [Full Text]
Khalil, H., Brunet, A., Thibodeau, J. (2005). A three-amino-acid-long HLA-DR{beta} cytoplasmic tail is sufficient to overcome ER retention of invariant-chain p35. J. Cell Sci. 118: 4679-4687 [Abstract] [Full Text]
Azar, G. A., Sekaly, R.-P., Thibodeau, J. (2005). A Defective Viral Superantigen-Presenting Phenotype in HLA-DR Transfectants Is Corrected by CIITA. J. Immunol. 174: 7548-7557 [Abstract] [Full Text]
Chamuleau, M. E. D., Souwer, Y., van Ham, S. M., Zevenbergen, A., Westers, T. M., Berkhof, J., Meijer, C. J. L. M., van de Loosdrecht, A. A., Ossenkoppele, G. J. (2004). Class II-Associated Invariant Chain Peptide Expression on Myeloid Leukemic Blasts Predicts Poor Clinical Outcome. Cancer Res. 64: 5546-5550 [Abstract] [Full Text]
Gregers, T. F., Fleckenstein, B., Vartdal, F., Roepstorff, P., Bakke, O., Sandlie, I. (2003). MHC class II loading of high or low affinity peptides directed by Ii/peptide fusion constructs: implications for T cell activation. Int Immunol 15: 1291-1299 [Abstract] [Full Text]
Khalil, H., Brunet, A., Saba, I., Terra, R., Sekaly, R. P., Thibodeau, J. (2003). The MHC class II {beta} chain cytoplasmic tail overcomes the invariant chain p35-encoded endoplasmic reticulum retention signal. Int Immunol 15: 1249-1263 [Abstract] [Full Text]
Huang, J. C., Han, M., Minguela, A., Pastor, S., Qadri, A., Ward, E. S. (2003). T Cell Recognition of Distinct Peptide:I-Au Conformers in Murine Experimental Autoimmune Encephalomyelitis. J. Immunol. 171: 2467-2477 [Abstract] [Full Text]
Chalouni, C., Banchereau, J., Vogt, A. B., Pascual, V., Davoust, J. (2003). Human germinal center B cells differ from naive and memory B cells by their aggregated MHC class II-rich compartments lacking HLA-DO. Int Immunol 15: 457-466 [Abstract] [Full Text]
Koonce, C. H., Wutz, G., Robertson, E. J., Vogt, A. B., Kropshofer, H., Bikoff, E. K. (2003). DM Loss in k Haplotype Mice Reveals Isotype-Specific Chaperone Requirements. J. Immunol. 170: 3751-3761 [Abstract] [Full Text]
Matza, D., Lantner, F., Bogoch, Y., Flaishon, L., Hershkoviz, R., Shachar, I. (2002). Invariant chain induces B cell maturation in a process that is independent of its chaperonic activity. Proc. Natl. Acad. Sci. USA 10.1073/pnas.052703299v1 [Abstract] [Full Text]
Chou, C.-L., Sadegh-Nasseri, S. (2000). HLA-DM Recognizes the Flexible Conformation of Major Histocompatibility Complex Class II. JEM 192: 1697-1706 [Abstract] [Full Text]
Barnhart, M. M., Pinkner, J. S., Soto, G. E., Sauer, F. G., Langermann, S., Waksman, G., Frieden, C., Hultgren, S. J. (2000). PapD-like chaperones provide the missing information for folding of pilin proteins. Proc. Natl. Acad. Sci. USA 10.1073/pnas.130183897v1 [Abstract] [Full Text]
Inaba, K., Turley, S., Iyoda, T., Yamaide, F., Shimoyama, S., e Sousa, C. R., Germain, R. N., Mellman, I., Steinman, R. M. (2000). The Formation of Immunogenic Major Histocompatibility Complex Class II-Peptide Ligands in Lysosomal Compartments of Dendritic Cells Is Regulated by Inflammatory Stimuli. JEM 191: 927-936 [Abstract] [Full Text]
Driessen, C., Bryant, R. A.R., Lennon-Dumenil, A.-M., Villadangos, J. A., Bryant, P. W., Shi, G.-P., Chapman, H. A., Ploegh, H. L. (1999). Cathepsin S Controls the Trafficking and Maturation of MHC Class II Molecules in Dendritic Cells. JCB 147: 775-790 [Abstract] [Full Text]
Eynon, E. E., Schlax, C., Pieters, J. (1999). A Secreted Form of the Major Histocompatibility Complex Class II-associated Invariant Chain Inhibiting T Cell Activation. J. Biol. Chem. 274: 26266-26271 [Abstract] [Full Text]
Ashman, J. B., Miller, J. (1999). A Role for the Transmembrane Domain in the Trimerization of the MHC Class II-Associated Invariant Chain. J. Immunol. 163: 2704-2712 [Abstract] [Full Text]
Kenty, G., Bikoff, E. K. (1999). 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. J. Immunol. 163: 232-241 [Abstract] [Full Text]
Qadri, A., Thatte, J., Radu, C. G., Ober, B., Ward, E. S. (1999). Characterization of the interaction of a TCR {alpha} chain variable domain with MHC II I-A molecules. Int Immunol 11: 967-977 [Abstract] [Full Text]
Thayer, W. P., Ignatowicz, L., Weber, D. A., Jensen, P. E. (1999). Class II-Associated Invariant Chain Peptide-Independent Binding of Invariant Chain to Class II MHC molecules. J. Immunol. 162: 1502-1509 [Abstract] [Full Text]
Wilson, N. A., Wolf, P., Ploegh, H., Ignatowicz, L., Kappler, J., Marrack, P. (1998). Invariant Chain Can Bind MHC Class II at a Site Other Than the Peptide Binding Groove. J. Immunol. 161: 4777-4784 [Abstract] [Full Text]
Castellino, F., Zappacosta, F., Coligan, J. E., Germain, R. N. (1998). Large Protein Fragments as Substrates for Endocytic Antigen Capture by MHC Class II Molecules. J. Immunol. 161: 4048-4057 [Abstract] [Full Text]
Deussing, J., Roth, W., Saftig, P., Peters, C., Ploegh, H. L., Villadangos, J. A. (1998). Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation. Proc. Natl. Acad. Sci. USA 95: 4516-4521 [Abstract] [Full Text]
Bikoff, E. K., Kenty, G., Van Kaer, L. (1998). Distinct Peptide Loading Pathways for MHC Class II Molecules Associated with Alternative Ii Chain Isoforms. J. Immunol. 160: 3101-3110 [Abstract] [Full Text]
Siebenkotten, I. M., Carstens, C., Koch, N. (1998). Identification of a Sequence That Mediates Promiscuous Binding of Invariant Chain to MHC Class II Allotypes. J. Immunol. 160: 3355-3362 [Abstract] [Full Text]
Barois, N, Forquet, F, Davoust, J (1998). Actin microfilaments control the MHC class II antigen presentation pathway in B cells. J. Cell Sci. 111: 1791-1800 [Abstract]
Fling, S. P., Rak, J., Muczynski, K. A., Arp, B., Pious, D. (1997). Novel Mutants Define Genes Required for the Expression of Human Histocompatibility Leukocyte Antigen DM: Evidence for Loci on Human Chromosome 6p. JEM 186: 1469-1480 [Abstract] [Full Text]
Villadangos, J. A., Riese, R. J., Peters, C., Chapman, H. A., Ploegh, H. L. (1997). Degradation of Mouse Invariant Chain: Roles of Cathepsins S and D and the Influence of Major Histocompatibility Complex Polymorphism. JEM 186: 549-560 [Abstract] [Full Text]
Barois, N., Forquet, F., Davoust, J. (1997). Selective Modulation of the Major Histocompatibility Complex Class II Antigen Presentation Pathway following B Cell Receptor Ligation and Protein Kinase C Activation. J. Biol. Chem. 272: 3641-3647 [Abstract] [Full Text]
Zhong, G., Romagnoli, P., Germain, R. N. (1997). Related Leucine-based Cytoplasmic Targeting Signals in Invariant Chain and Major Histocompatibility Complex Class II Molecules Control Endocytic Presentation of Distinct Determinants in a Single Protein. JEM 185: 429-438 [Abstract] [Full Text]
Denzin, L. K., Hammond, C., Cresswell, P. (1996). HLA-DM Interactions with Intermediates in HLA-DR Maturation and a Role for HLA-DM in Stabilizing Empty HLA-DR Molecules. JEM 184: 2153-2166 [Abstract] [Full Text]
Kropshofer, H., Vogt, A. B., Stern, L. J., H�mmerling, G�n. J. (1995). Self-Release of CLIP in Peptide Loading of HLA-DR Molecules. Science 270: 1357-1359 [Abstract]
Brunet, A., Samaan, A., Deshaies, F., Kindt, T. J., Thibodeau, J. (2000). Functional Characterization of a Lysosomal Sorting Motif in the Cytoplasmic Tail of HLA-DObeta. J. Biol. Chem. 275: 37062-37071 [Abstract] [Full Text]
Honey, K., Duff, M., Beers, C., Brissette, W. H., Elliott, E. A., Peters, C., Maric, M., Cresswell, P., Rudensky, A. (2001). Cathepsin S Regulates the Expression of Cathepsin L and the Turnover of gamma -Interferon-inducible Lysosomal Thiol Reductase in B Lymphocytes. J. Biol. Chem. 276: 22573-22578 [Abstract] [Full Text]
Faubert, A., Samaan, A., Thibodeau, J. (2002). Functional Analysis of Tryptophans alpha 62 and beta 120 on HLA-DM. J. Biol. Chem. 277: 2750-2755 [Abstract] [Full Text]
Matza, D., Lantner, F., Bogoch, Y., Flaishon, L., Hershkoviz, R., Shachar, I. (2002). Invariant chain induces B cell maturation in a process that is independent of its chaperonic activity. Proc. Natl. Acad. Sci. USA 99: 3018-3023 [Abstract] [Full Text]
Barnhart, M. M., Pinkner, J. S., Soto, G. E., Sauer, F. G., Langermann, S., Waksman, G., Frieden, C., Hultgren, S. J. (2000). From the Cover: PapD-like chaperones provide the missing information for folding of pilin proteins. Proc. Natl. Acad. Sci. USA 97: 7709-7714 [Abstract] [Full Text]