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Science 1 March 1996:
Vol. 271. no. 5253, pp. 1278 - 1281
DOI: 10.1126/science.271.5253.1278
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Reports

Antigen Presentation and T Cell Development in H2-M-Deficient Mice

Wai-Ping Fung-Leung, Charles D. Surh, Monika Liljedahl, Jesse Pang, Didier Leturcq, Per A. Peterson, Susan R. Webb, Lars Karlsson *

HLA-DM (DM) facilitates peptide loading of major histocompatibility complex class II molecules in human cell lines. Mice lacking functional H2-M, the mouse equivalent of DM, have normal amounts of class II molecules at the cell surface, but most of these are associated with invariant chain-derived CLIP peptides. These mice contain large numbers of CD4+ T cells, which is indicative of positive selection in the thymus. Their CD4+ cells were unresponsive to self H2-M-deficient antigen-presenting cells (APCs) but were hyperreactive to wild-type APCs. H2-M-deficient APCs failed to elicit proliferative responses from wild-type T cells.

W.-P. Fung-Leung, J. Pang, D. Leturcq, P. A. Peterson, R. W. Johnson Pharmaceutical Research Institute, Suite 100, 3535 General Atomics Court, San Diego, CA 92121, USA.
C. D. Surh and S. R. Webb, Department of Immunology, IMM-4, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
M. Liljedahl and L. Karlsson, R. W. Johnson Pharmaceutical Research Institute at The Scripps Research Institute, IMM-23, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
* To whom correspondence should be addressed.


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C. D. Surh and J. Sprent (2000)
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J. Exp. Med. 192, 31-40
   Abstract »    Full Text »    PDF »
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P. Wong, A. W. Goldrath, and A. Y. Rudensky (2000)
J. Immunol. 164, 6252-6259
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The functional role of class II-associated invariant chain peptide (CLIP) in its ability to variably modulate immune responses.
P. Chaturvedi, R. Hengeveld, M. A. Zechel, E. Lee-Chan, and B. Singh (2000)
Int. Immunol. 12, 757-765
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Functional and Phenotypic Evidence for Presentation of E{alpha}52-68 Structurally Related Self-Peptide(s) in I-E{alpha}-Deficient Mice.
C. Viret and C. A. Janeway Jr. (2000)
J. Immunol. 164, 4627-4634
   Abstract »    Full Text »    PDF »
Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages.
G.-P. Shi, R. A.R. Bryant, R. Riese, S. Verhelst, C. Driessen, Z. Li, D. Bromme, H. L. Ploegh, and H. A. Chapman (2000)
J. Exp. Med. 191, 1177-1186
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Unexpected Reactivities of T Cells Selected by a Single MHC-Peptide Ligand.
N. Singh and L. Van Kaer (1999)
J. Immunol. 163, 3583-3591
   Abstract »    Full Text »    PDF »
NK and CTL Recognition of a Single Chain H-2Dd Molecule: Distinct Sites of H-2Dd Interact with NK and TCR.
D. H. Chung, J. Dorfman, D. Plaksin, K. Natarajan, I. M. Belyakov, R. Hunziker, J. A. Berzofsky, W. M. Yokoyama, M. G. Mage, and D. H. Margulies (1999)
J. Immunol. 163, 3699-3708
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Cd4+ T Cell Division in Irradiated Mice Requires Peptides Distinct from Those Responsible for Thymic Selection.
J. Bender, T. Mitchell, J. Kappler, and P. Marrack (1999)
J. Exp. Med. 190, 367-374
   Abstract »    Full Text »    PDF »
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.
G. Kenty and E. K. Bikoff (1999)
J. Immunol. 163, 232-241
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Conformational variants of class II MHC/peptide complexes induced by N- and C-terminal extensions of minimal peptide epitopes.
O. Rotzschke, K. Falk, J. Mack, J. M. Lau, G. Jung, and J. L. Strominger (1999)
PNAS 96, 7445-7450
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A Kinetic Threshold between Negative and Positive Selection Based on the Longevity of the T Cell Receptor-Ligand Complex.
C. B. Williams, D. L. Engle, G. J. Kersh, J. Michael White, and P. M. Allen (1999)
J. Exp. Med. 189, 1531-1544
   Abstract »    Full Text »    PDF »
Autoantigen-Independent Deletion of Diabetogenic CD4+ Thymocytes by Protective MHC Class II Molecules.
D. Schmidt, A. Amrani, J. Verdaguer, S. Bou, and P. Santamaria (1999)
J. Immunol. 162, 4627-4636
   Abstract »    Full Text »    PDF »
Peptide dependency of alloreactive CD4+ T cell responses.
S. K. Mendiratta, J.-P. Kovalik, S. Hong, N. Singh, W. D. Martin, and L. Van Kaer (1999)
Int. Immunol. 11, 351-360
   Abstract »    Full Text »    PDF »
HLA-DM and invariant chain are expressed by thyroid follicular cells, enabling the expression of compact DR molecules.
M. Catalfamo, L. Serradell, C. Roura-Mir, E. Kolkowski, M. Sospedra, M. Vives-Pi, F. Vargas-Nieto, R. Pujol-Borrell, and D. Jaraquemada (1999)
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H-2M molecules, like MHC class II molecules, are targeted to parasitophorous vacuoles of Leishmania-infected macrophages and internalized by amastigotes of L. amazonensis and L. mexicana.
J. Antoine, T Lang, E Prina, N Courret, and R Hellio (1999)
J. Cell Sci. 112, 2559-2570
   Abstract »    PDF »
A T Cell Receptor-specific Blockade of Positive Selection.
K. K. Baldwin, P. A. Reay, L. Wu, A. Farr, and M. M. Davis (1999)
J. Exp. Med. 189, 13-24
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Requirement for Diverse, Low-Abundance Peptides in Positive Selection of T Cells.
G. M. Barton and A. Y. Rudensky (1999)
Science 283, 67-70
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Differential Effects of Peptide Diversity and Stromal Cell Type in Positive and Negative Selection in the Thymus.
G. Anderson, K. M. Partington, and E. J. Jenkinson (1998)
J. Immunol. 161, 6599-6603
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Secondary Structure Composition and pH-dependent Conformational Changes of Soluble Recombinant HLA-DM.
R. Busch, Z. Reich, D. M. Zaller, V. Sloan, and E. D. Mellins (1998)
J. Biol. Chem. 273, 27557-27564
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Antagonist Peptide Selects Thymocytes Expressing a Class II Major Histocompatibility Complex-restricted T Cell Receptor into the CD8 Lineage.
A. Volkmann, T. Barthlott, S. Weiss, R. Frank, and B. Stockinger (1998)
J. Exp. Med. 188, 1083-1089
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Highly Restricted T Cell Repertoire Shaped by a Single Major Histocompatibility Complex-Peptide Ligand in the Presence of a Single Rearranged T Cell Receptor {beta} Chain.
Y. Fukui, O. Hashimoto, A. Inayoshi, T. Gyotoku, T. Sano, T. Koga, T. Gushima, and T. Sasazuki (1998)
J. Exp. Med. 188, 897-907
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Subtle conformational changes induced in major histocompatibility complex class II molecules by binding peptides.
A. V. Chervonsky, R. M. Medzhitov, L. K. Denzin, A. K. Barlow, A. Yu. Rudensky, and C. A. Janeway Jr. (1998)
PNAS 95, 10094-10099
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Impaired Antibody Responses in H-2Ab Mice.
S. Gustavsson, S. Hjulstrom-Chomez, B.-M. Lidstrom, N. Ahlborg, R. Andersson, and B. Heyman (1998)
J. Immunol. 161, 1765-1771
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Cathepsin L: Critical Role in Ii Degradation and CD4 T Cell Selection in the Thymus.
T. Nakagawa, W. Roth, P. Wong, A. Nelson, A. Farr, J. Deussing, J. A. Villadangos, H. Ploegh, C. Peters, and A. Y. Rudensky (1998)
Science 280, 450-453
   Abstract »    Full Text »
Natural and Engineered Disorders of Lymphocyte Development.
A. Fischer and B. Malissen (1998)
Science 280, 237-243
   Abstract »    Full Text »
Murine Cytomegalovirus Inhibits Interferon {gamma}-induced Antigen Presentation to CD4 T Cells by Macrophages Via Regulation of Expression of Major Histocompatibility Complex Class II-associated Genes.
M. T. Heise, M. Connick, and H. W. Virgin IV (1998)
J. Exp. Med. 187, 1037-1046
   Abstract »    Full Text »    PDF »
Mtv-1 Superantigen Trafficks Independently of Major Histocompatibility Complex Class II Directly to the B-Cell Surface by the Exocytic Pathway.
M. E. Grigg, C. W. McMahon, S. Morkowski, A. Y. Rudensky, and A. M. Pullen (1998)
J. Virol. 72, 2577-2588
   Abstract »    Full Text »    PDF »
Distinct Peptide Loading Pathways for MHC Class II Molecules Associated with Alternative Ii Chain Isoforms.
E. K. Bikoff, G. Kenty, and L. Van Kaer (1998)
J. Immunol. 160, 3101-3110
   Abstract »    Full Text »    PDF »
Discoordinate Surface Expression of IFN-{gamma}-Induced HLA Class II Proteins in Nonprofessional Antigen-Presenting Cells with Absence of DM and Class II Colocalization.
K. A. Muczynski, S. K. Anderson, and D. Pious (1998)
J. Immunol. 160, 3207-3216
   Abstract »    Full Text »    PDF »
Identification of a Sequence That Mediates Promiscuous Binding of Invariant Chain to MHC Class II Allotypes.
I. M. Siebenkotten, C. Carstens, and N. Koch (1998)
J. Immunol. 160, 3355-3362
   Abstract »    Full Text »    PDF »
Invariant Chain-independent Function of H-2M in the Formation of Endogenous Peptide-Major Histocompatibility Complex Class II Complexes In Vivo.
S. Kovats, C. E. Grubin, S. Eastman, P. deRoos, A. Dongre, L. V. Kaer, and A. Y. Rudensky (1998)
J. Exp. Med. 187, 245-251
   Abstract »    Full Text »    PDF »
Cutting Edge: A Critical, Invariant Chain-Independent Role for H2-M in Antigen Presentation.
K. Swier, D. R. Brown2, J. J. Bird, W. D. Martin, L. V. Kaer, and S. L. Reiner (1998)
J. Immunol. 160, 540-544
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Rejection of Allogeneic and Syngeneic But Not MHC Class I-Deficient Tumor Grafts by MHC Class I-Deficient Mice.
S. Freland, B. J. Chambers, M. Andersson, L. Van Kaer, and H.-G. Ljunggren (1998)
J. Immunol. 160, 572-579
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MHC Class II Expression in Double Mutant Mice Lacking Invariant Chain and DM Functions.
G. Kenty, W. D. Martin, L. Van Kaer, and E. K. Bikoff (1998)
J. Immunol. 160, 606-614
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Aberrant Intermolecular Disulfide Bonding in a Mutant HLA-DM Molecule: Implications for Assembly, Maturation, and Function.
R. Busch, R. C. Doebele, E. von Scheven, J. Fahrni, and E. D. Mellins (1998)
J. Immunol. 160, 734-743
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How Many Thymocytes Audition for Selection?.
M. Merkenschlager, D. Graf, M. Lovatt, U. Bommhardt, R. Zamoyska, and A. G. Fisher (1997)
J. Exp. Med. 186, 1149-1158
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Functionality of major histocompatibility complex class II molecules in mice doubly deficient for invariant chain and H-2M complexes.
S. Tourne, T. Miyazaki, P. Wolf, H. Ploegh, C. Benoist, and D. Mathis (1997)
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Degradation of Mouse Invariant Chain: Roles of Cathepsins S and D and the Influence of Major Histocompatibility Complex Polymorphism.
J. A. Villadangos, R. J. Riese, C. Peters, H. A. Chapman, and H. L. Ploegh (1997)
J. Exp. Med. 186, 549-560
   Abstract »    Full Text »    PDF »
Enhanced Intracellular Dissociation of Major Histocompatibility Complex Class I-associated Peptides: A Mechanism for Optimizing the Spectrum of Cell Surface-Presented Cytotoxic T Lymphocyte Epitopes.
A. J.A.M. Sijts and E. G. Pamer (1997)
J. Exp. Med. 185, 1403-1412
   Abstract »    Full Text »    PDF »
Quantitative Impact of Thymic Clonal Deletion on the T Cell Repertoire.
J. P.M. van Meerwijk, S. Marguerat, R. K. Lees, R. N. Germain, B.J. Fowlkes, and H. R. MacDonald (1997)
J. Exp. Med. 185, 377-384
   Abstract »    Full Text »    PDF »
Positive Selection of T Cells Induced by Viral Delivery of Neopeptides to the Thymus.
N. Nakano, R. Rooke, C. Benoist, and D. Mathis (1997)
Science 275, 678-683
   Abstract »    Full Text »
HLA-DM Interactions with Intermediates in HLA-DR Maturation and a Role for HLA-DM in Stabilizing Empty HLA-DR Molecules.
L. K. Denzin, C. Hammond, and P. Cresswell (1996)
J. Exp. Med. 184, 2153-2166
   Abstract »    Full Text »    PDF »
H2-Mbeta 1 and H2-Mbeta 2 Heterodimers Equally Promote CLIP Removal in I-Aq Molecules from Autoimmune-prone DBA/1 Mice.
W. Walter, C. Scheuer, M. Loos, T. E. Reichert, and M. J. Maeurer (2001)
J. Biol. Chem. 276, 11086-11091
   Abstract »    Full Text »    PDF »
Functional Analysis of Tryptophans alpha 62 and beta 120 on HLA-DM.
A. Faubert, A. Samaan, and J. Thibodeau (2002)
J. Biol. Chem. 277, 2750-2755
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Paradoxical intrathymic positive selection in mice with only a covalently presented agonist peptide.
C. Viret, X. He, and C. A. Janeway Jr. (2001)
PNAS 98, 9243-9248
   Abstract »    Full Text »    PDF »
Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact.
Y. Fukui, T. Oono, J.-P. Cabaniols, K. Nakao, K. Hirokawa, A. Inayoshi, T. Sanui, J. Kanellopoulos, E. Iwata, M. Noda, et al. (2000)
PNAS 97, 13760-13765
   Abstract »    Full Text »    PDF »
Regulated Expression of Human Histocompatibility Leukocyte Antigen (HLA)-DO During Antigen-dependent and Antigen-independent Phases of B Cell Development.
X. Chen, O. Laur, T. Kambayashi, S. Li, R. A. Bray, D. A. Weber, L. Karlsson, and P. E. Jensen (2002)
J. Exp. Med. 195, 1053-1062
   Abstract »    Full Text »    PDF »


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