DM Determines the Cryptic and Immunodominant Fate of T Cell Epitopes

doi:10.1084/jem.192.6.781

Published online 11 September 2000.

This Article

	Full Text
	Full Text (PDF)
	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 Nanda, N. K.
	Articles by Sant, A. J.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Nanda, N. K.
	Articles by Sant, A. J.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0022-1007/2000/9/781/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 6, September 18, 2000 781-788

Original Article

DM Determines the Cryptic and Immunodominant Fate of T Cell Epitopes

Navreet K. Nanda^a and Andrea J. Sant^b
^a Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois 60612
^b Department of Pathology, University of Chicago, Chicago, Illinois 60637

Correspondence to: Navreet K. Nanda, Department of Microbiology and Immunology, 835 South Wolcott Ave., Chicago, IL 60612-7344. Tel:312-413-1446 Fax:312-996-6415 E-mail:navreetn{at}uic.edu.

The ability of the immune system to focus T cell responses againsta select number of potential epitopes of a complex antigen istermed immunodominance. Epitopes that trigger potent T cellactivation, after in vivo priming, are classified as immunodominant.By contrast, determinants that fail to elicit any response arecalled cryptic. DM, a major histocompatibility complex (MHC)heterodimer, plays a pivotal role in the presentation of MHCclass II–restricted epitopes by catalyzing the exchangeof class II–associated invariant chain peptide with theantigen-derived peptides within the MHC class II binding groove.Using L cells transfected with genes for MHC class II, invariantchain, and DM, we have studied the contribution of DM in thepresentation of two cryptic (peptide 11–25 and peptide20–35) and one dominant (peptide 106–116) epitopeof hen egg white lysozyme (HEL). Cells lacking DM heterodimersefficiently display the determinants HEL 11–25 and HEL20–35 to T cells. Strikingly, however, cells expressingDM are severely compromised in their ability to present thecryptic HEL 11–25/A^d and 20–35/A^d epitopes. DM-mediatedantagonism of HEL 11–25/A^d and 20–35/A^d presentationcould thus be central to 11–25/A^d and 20–35/A^d beingcryptic epitopes in the HEL system. Interestingly, the displayof the immunodominant epitope of HEL, 106–116/E^d, andof a dominant epitope of sperm whale myoglobin (SWM), 102–118/A^d,is entirely dependent on the expression of DM. Thus, cells lackingDM molecules are unable to efficiently express HEL 106–116/E^dand SWM 102–118/A^d determinants. We conclude that theDM heterodimers direct the immunodominant and cryptic fate ofantigenic epitopes in vivo.

Key Words: antigen determinant, antigen processing, H-2M, immunodominance,major histocompatibility complex class II

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:

Weaver, J. M., Lazarski, C. A., Richards, K. A., Chaves, F. A., Jenks, S. A., Menges, P. R., Sant, A. J. (2008). Immunodominance of CD4 T Cells to Foreign Antigens Is Peptide Intrinsic and Independent of Molecular Context: Implications for Vaccine Design. J. Immunol. 181: 3039-3048 [Abstract] [Full Text]
Huang, S., Gilfillan, S., Kim, S., Thompson, B., Wang, X., Sant, A. J., Fremont, D. H., Lantz, O., Hansen, T. H. (2008). MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells. J. Exp. Med. 205: 1201-1211 [Abstract] [Full Text]
Larkin, J. III, Rankin, A. L., Picca, C. C., Riley, M. P., Jenks, S. A., Sant, A. J., Caton, A. J. (2008). CD4+CD25+ Regulatory T Cell Repertoire Formation Shaped by Differential Presentation of Peptides from a Self-Antigen. J. Immunol. 180: 2149-2157 [Abstract] [Full Text]
Menges, P. R., Jenks, S. A., Bikoff, E. K., Friedmann, D. R., Knowlden, Z. A. G., Sant, A. J. (2008). An MHC Class II Restriction Bias in CD4 T Cell Responses toward I-A Is Altered to I-E in DM-Deficient Mice. J. Immunol. 180: 1619-1633 [Abstract] [Full Text]
Rinderknecht, C. H., Belmares, M. P., Catanzarite, T. L. W., Bankovich, A. J., Holmes, T. H., Garcia, K. C., Nanda, N. K., Busch, R., Kovats, S., Mellins, E. D. (2007). Posttranslational Regulation of I-Ed by Affinity for CLIP. J. Immunol. 179: 5907-5915 [Abstract] [Full Text]
Grotenbreg, G. M., Nicholson, M. J., Fowler, K. D., Wilbuer, K., Octavio, L., Yang, M., Chakraborty, A. K., Ploegh, H. L., Wucherpfennig, K. W. (2007). Empty Class II Major Histocompatibility Complex Created by Peptide Photolysis Establishes the Role of DM in Peptide Association. J. Biol. Chem. 282: 21425-21436 [Abstract] [Full Text]
Lazarski, C. A., Chaves, F. A., Sant, A. J. (2006). The impact of DM on MHC class II-restricted antigen presentation can be altered by manipulation of MHC-peptide kinetic stability. J. Exp. Med. 203: 1319-1328 [Abstract] [Full Text]
Nicholson, M. J., Moradi, B., Seth, N. P., Xing, X., Cuny, G. D., Stein, R. L., Wucherpfennig, K. W. (2006). Small Molecules That Enhance the Catalytic Efficiency of HLA-DM. J. Immunol. 176: 4208-4220 [Abstract] [Full Text]
Nanda, N. K., Bikoff, E. K. (2005). DM Peptide-Editing Function Leads to Immunodominance in CD4 T Cell Responses In Vivo. J. Immunol. 175: 6473-6480 [Abstract] [Full Text]
Zhu, H., Liu, K., Cerny, J., Imoto, T., Moudgil, K. D. (2005). Insertion of the Dibasic Motif in the Flanking Region of a Cryptic Self-Determinant Leads to Activation of the Epitope-Specific T Cells. J. Immunol. 175: 2252-2260 [Abstract] [Full Text]
Bellemare-Pelletier, A., Tremblay, J., Beaulieu, S., Boulassel, M.-R., Routy, J.-P., Massie, B., Lapointe, R., Thibodeau, J. (2005). HLA-DO transduced in human monocyte-derived dendritic cells modulates MHC class II antigen processing. J. Leukoc. Biol. 78: 95-105 [Abstract] [Full Text]
Ayyoub, M., Merlo, A., Hesdorffer, C. S., Rimoldi, D., Speiser, D., Cerottini, J.-C., Chen, Y.-T., Old, L. J., Stevanovic, S., Valmori, D. (2005). CD4+ T Cell Responses to SSX-4 in Melanoma Patients. J. Immunol. 174: 5092-5099 [Abstract] [Full Text]
Howarth, M., Williams, A., Tolstrup, A. B., Elliott, T. (2004). Tapasin enhances MHC class I peptide presentation according to peptide half-life. Proc. Natl. Acad. Sci. USA 101: 11737-11742 [Abstract] [Full Text]
Durai, M., Kim, H. R., Moudgil, K. D. (2004). The Regulatory C-Terminal Determinants within Mycobacterial Heat Shock Protein 65 Are Cryptic and Cross-Reactive with the Dominant Self Homologs: Implications for the Pathogenesis of Autoimmune Arthritis. J. Immunol. 173: 181-188 [Abstract] [Full Text]
Yeung, V. P., Chang, J., Miller, J., Barnett, C., Stickler, M., Harding, F. A. (2004). Elimination of an Immunodominant CD4+ T Cell Epitope in Human IFN-{beta} Does Not Result in an In Vivo Response Directed at the Subdominant Epitope. J. Immunol. 172: 6658-6665 [Abstract] [Full Text]
Anderson, M. W., Gorski, J. (2003). Cutting Edge: TCR Contacts as Anchors: Effects on Affinity and HLA-DM Stability. J. Immunol. 171: 5683-5687 [Abstract] [Full Text]
Lovitch, S. B., Petzold, S. J., Unanue, E. R. (2003). Cutting Edge: H-2DM Is Responsible for the Large Differences in Presentation Among Peptides Selected by I-Ak During Antigen Processing. J. Immunol. 171: 2183-2186 [Abstract] [Full Text]
Lich, J. D., Jayne, J. A., Zhou, D., Elliott, J. F., Blum, J. S. (2003). Editing of an Immunodominant Epitope of Glutamate Decarboxylase by HLA-DM. J. Immunol. 171: 853-859 [Abstract] [Full Text]
CLARK, M. R., MASSENBURG, D., ZHANG, M., SIEMASKO, K. (2003). Molecular Mechanisms of B Cell Antigen Receptor Trafficking. Ann. N. Y. Acad. Sci. 987: 26-37 [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]
Belmares, M. P., Busch, R., Wucherpfennig, K. W., McConnell, H. M., Mellins, E. D. (2002). Structural Factors Contributing to DM Susceptibility of MHC Class II/Peptide Complexes. J. Immunol. 169: 5109-5117 [Abstract] [Full Text]
Tompkins, S. M., Padilla, J., Dal Canto, M. C., Ting, J. P.-Y., Van Kaer, L., Miller, S. D. (2002). De Novo Central Nervous System Processing of Myelin Antigen Is Required for the Initiation of Experimental Autoimmune Encephalomyelitis. J. Immunol. 168: 4173-4183 [Abstract] [Full Text]
Alfonso, C., Han, J.-O., Williams, G. S., Karlsson, L. (2001). The Impact of H2-DM on Humoral Immune Responses. J. Immunol. 167: 6348-6355 [Abstract] [Full Text]
Bikoff, E. K., Wutz, G., Kenty, G. A., Koonce, C. H., Robertson, E. J. (2001). Relaxed DM Requirements During Class II Peptide Loading and CD4+ T Cell Maturation in BALB/c Mice. J. Immunol. 166: 5087-5098 [Abstract] [Full Text]
Chou, C.-L., Sadegh-Nasseri, S. (2000). HLA-DM Recognizes the Flexible Conformation of Major Histocompatibility Complex Class II. J. Exp. Med. 192: 1697-1706 [Abstract] [Full Text]