Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells

doi:10.1084/jem.176.1.89

This Article

	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 Killeen, N.
	Articles by Littman, D. R.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Killeen, N.
	Articles by Littman, D. R.


Social Bookmarking

	What's this?

ARTICLES

Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells

N Killeen, A Moriarty, HS Teh and DR Littman
Department of Microbiology and Immunology, University of California, San Francisco 94143-0414.

The interaction of the T cell surface glycoprotein CD8 with major histocompatibility complex (MHC) class I molecules on target cells is required for effective T cell activation. Mutations in the alpha 3 domain of the MHC class I molecule can disrupt binding to CD8, yet leave antigen presentation unaffected. Here we show that such a mutation can interfere with positive and negative selection of T cells bearing T cell receptors (TCRs) that interact specifically with the mutant class I molecule. Autoreactive T cells in male mice expressing a transgenic TCR specific for the male antigen H-Y and H-2Db were not deleted in the context of a transgenic Db molecule bearing a mutation at residue 227. Similarly, CD8+ cells were not positively selected in female mice expressing both the TCR and mutant class I transgenes. Endogenous MHC class I molecules were competent to bind CD8, but were unable to rescue the defect, indicating a requirement for coordinate recognition of antigen/MHC by a complex of the TCR and CD8 coreceptor for both positive and negative selection of thymocytes.
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:

Belyakov, I. M., Kozlowski, S., Mage, M., Ahlers, J. D., Boyd, L. F., Margulies, D. H., Berzofsky, J. A. (2007). Role of {alpha}3 domain of class I MHC molecules in the activation of high- and low-avidity CD8+ CTLs. Int Immunol 19: 1413-1420 [Abstract] [Full Text]
Ferreira, C., Furmanski, A., Millrain, M., Bartok, I., Guillaume, P., Lees, R., Simpson, E., MacDonald, H. R., Dyson, J. (2006). TCR-{alpha} CDR3 Loop Audition Regulates Positive Selection. J. Immunol. 177: 2477-2485 [Abstract] [Full Text]
Kerry, S. E., Buslepp, J., Cramer, L. A., Maile, R., Hensley, L. L., Nielsen, A. I., Kavathas, P., Vilen, B. J., Collins, E. J., Frelinger, J. A. (2003). Interplay between TCR Affinity and Necessity of Coreceptor Ligation: High-Affinity Peptide-MHC/TCR Interaction Overcomes Lack of CD8 Engagement. J. Immunol. 171: 4493-4503 [Abstract] [Full Text]
Hutchinson, S. L., Wooldridge, L., Tafuro, S., Laugel, B., Glick, M., Boulter, J. M., Jakobsen, B. K., Price, D. A., Sewell, A. K. (2003). The CD8 T Cell Coreceptor Exhibits Disproportionate Biological Activity at Extremely Low Binding Affinities. J. Biol. Chem. 278: 24285-24293 [Abstract] [Full Text]
Naeher, D., Luescher, I. F., Palmer, E. (2002). A Role for the {alpha}-Chain Connecting Peptide Motif in Mediating TCR-CD8 Cooperation. J. Immunol. 169: 2964-2970 [Abstract] [Full Text]
Gao, G. F., Willcox, B. E., Wyer, J. R., Boulter, J. M., O'Callaghan, C. A., Maenaka, K., Stuart, D. I., Jones, E. Y., Van Der Merwe, P. A., Bell, J. I., Jakobsen, B. K. (2000). Classical and Nonclassical Class I Major Histocompatibility Complex Molecules Exhibit Subtle Conformational Differences That Affect Binding to CD8alpha alpha. J. Biol. Chem. 275: 15232-15238 [Abstract] [Full Text]
Kobayashi, S., Yoshida, K., Ward, J. M., Letterio, J. J., Longenecker, G., Yaswen, L., Mittleman, B., Mozes, E., Roberts, A. B., Karlsson, S., Kulkarni, A. B. (1999). {beta}2-Microglobulin-Deficient Background Ameliorates Lethal Phenotype of the TGF-{beta}1 Null Mouse. J. Immunol. 163: 4013-4019 [Abstract] [Full Text]
Maroto, R., Shen, X., Konig, R. (1999). Requirement for Efficient Interactions Between CD4 and MHC Class II Molecules for Survival of Resting CD4+ T Lymphocytes In Vivo and for Activation-Induced Cell Death. J. Immunol. 162: 5973-5980 [Abstract] [Full Text]
Arsov, I., Vukmanovic, S. (1999). Dual MHC Class I and Class II Restriction of a Single T Cell Receptor: Distinct Modes of Tolerance Induction by Two Classes of Autoantigens. J. Immunol. 162: 2008-2015 [Abstract] [Full Text]
Yelon, D., Schaefer, K. L., Berg, L. J. (1999). Alterations in CD4-Binding Regions of the MHC Class II Molecule I-Ek Do Not Impede CD4+ T Cell Development. J. Immunol. 162: 1348-1358 [Abstract] [Full Text]
Gilfillan, S., Shen, X., Konig3, R. (1998). Selection and Function of CD4+ T Lymphocytes in Transgenic Mice Expressing Mutant MHC Class II Molecules Deficient in Their Interaction with CD4. J. Immunol. 161: 6629-6637 [Abstract] [Full Text]
Smith, P. A., Potter, T. A. (1998). Alloreactive T Cells That Do Not Require TCR and CD8 Coengagement Are Present in Naive Mice and Contribute to Graft Rejection. J. Immunol. 160: 5382-5389 [Abstract] [Full Text]
Riberdy, J. M., Mostaghel, E., Doyle, C. (1998). Disruption of the CD4-major histocompatibility complex class II interaction blocks the development of CD4+ T cells in vivo. Proc. Natl. Acad. Sci. USA 95: 4493-4498 [Abstract] [Full Text]
Kulig, K., Nandi, D., Bacik, I., Monaco, J. J., Vukmanovic, S. (1998). Physical and Functional Association of the Major Histocompatibility Complex Class I Heavy Chain alpha 3 Domain with the Transporter Associated with Antigen Processing. J. Exp. Med. 187: 865-874 [Abstract] [Full Text]
Teh, H.-S., Motyka, B., Teh, S.-J. (1998). Positive Selection of Thymocytes Expressing the Same TCR by Different MHC Ligands Results in the Production of Functionally Distinct Thymocytes Distinguished by Differential Expression of the Heat Stable Antigen. J. Immunol. 160: 718-727 [Abstract] [Full Text]
Sebzda, E, Wallace, V., Mayer, J, Yeung, R., Mak, T., Ohashi, P. (1994). Positive and negative thymocyte selection induced by different concentrations of a single peptide. Science 263: 1615-1618 [Abstract]
Penninger, J, Kishihara, K, Molina, T, Wallace, V., Timms, E, Hedrick, S., Mak, T. (1993). Requirement for tyrosine kinase p56lck for thymic development of transgenic gamma delta T cells. Science 260: 358-361 [Abstract]