The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Snyder, M. R.
Right arrow Articles by Goronzy, J. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Snyder, M. R.
Right arrow Articles by Goronzy, J. J.
The Journal of Immunology, 2004, 173: 3725-3731.
Copyright © 2004 by The American Association of Immunologists

Stimulatory Killer Ig-Like Receptors Modulate T Cell Activation through DAP12-Dependent and DAP12-Independent Mechanisms1

Melissa R. Snyder, Takako Nakajima, Paul J. Leibson, Cornelia M. Weyand and Jörg J. Goronzy2

Departments of Medicine and Immunology, Mayo Clinic, Rochester, MN 55905

Stimulatory killer Ig-like receptors (KIRs) are expressed by various lymphocytes, including NK cells and subsets of T cells. In NK cells, KIRs associate with the adapter molecule KARAP/DAP12, which confers the ability to function as an independent activation unit. The function of KIRs and killer cell activating receptor-associated protein (KARAP)/DAP12 in T cells is unclear. By flow cytometry, we demonstrated that CD4+CD28null T cells heterogeneously express KIRs and/or KARAP/DAP12. In clones that lacked expression of KARAP/DAP12, the stimulatory KIR KIR2DS2 signaled through the JNK pathway, but did not activate the ERK pathway. However, in the presence of KARAP/DAP12, stimulation through KIR2DS2 led to phosphorylation of both JNK and ERK. Transfection experiments confirmed that KIR2DS2-mediated ERK phosphorylation was dependent on KARAP/DAP12. The differential signaling of KIR2DS2 through association with alternative adapter molecules resulted in differential regulation of cellular activity. In clones that lacked expression of KARAP/DAP12, stimulation of KIR2DS2 did not induce cytotoxicity. However, KIR2DS2 did augment suboptimal TCR stimulation, leading to enhanced IFN-{gamma} production. In clones that expressed KARAP/DAP12, KIR2DS2 directly activated both cytotoxicity and IFN-{gamma} production without the need for TCR-derived signals. The function of stimulatory KIRs in T cells is determined by the expression of the appropriate adapter molecule. Expression of KARAP/DAP12 is sufficient to convert a costimulatory KIR into a stimulatory molecule. These differing functions mediated by alternative signaling pathways have implications for the pathogenesis of diseases such as rheumatoid arthritis and acute coronary syndromes, in which aberrant expression of KIRs on T cells is frequently observed.




This article has been cited by other articles:


Home page
 J. Virol.Home page
B. R. Long, L. C. Ndhlovu, J. R. Oksenberg, L. L. Lanier, F. M. Hecht, D. F. Nixon, and J. D. Barbour
Conferral of Enhanced Natural Killer Cell Function by KIR3DS1 in Early Human Immunodeficiency Virus Type 1 Infection
J. Virol., May 15, 2008; 82(10): 4785 - 4792.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Remtoula, A. Bensussan, and A. Marie-Cardine
Cutting Edge: Selective Expression of Inhibitory or Activating Killer Cell Ig-Like Receptors in Circulating CD4+ T Lymphocytes
J. Immunol., March 1, 2008; 180(5): 2767 - 2771.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
V. Pascal, E. Yamada, M. P. Martin, G. Alter, M. Altfeld, J. A. Metcalf, M. W. Baseler, J. W. Adelsberger, M. Carrington, S. K. Anderson, et al.
Detection of KIR3DS1 on the Cell Surface of Peripheral Blood NK Cells Facilitates Identification of a Novel Null Allele and Assessment of KIR3DS1 Expression during HIV-1 Infection
J. Immunol., August 1, 2007; 179(3): 1625 - 1633.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
S. Pryshchep, K. Sato, J. J. Goronzy, and C. M. Weyand
T Cell Recognition and Killing of Vascular Smooth Muscle Cells in Acute Coronary Syndrome
Circ. Res., May 12, 2006; 98(9): 1168 - 1176.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. R. Ortaldo, R. Winkler-Pickett, J. Wigginton, M. Horner, E. W. Bere, A. T. Mason, N. Bhat, J. Cherry, M. Sanford, D. L. Hodge, et al.
Regulation of ITAM-positive receptors: role of IL-12 and IL-18
Blood, February 15, 2006; 107(4): 1468 - 1475.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
J. J. GORONZY, G. HENEL, H. SAWAI, K. SINGH, E. B. LEE, S. PRYSHCHEP, and C. M. WEYAND
Costimulatory Pathways in Rheumatoid Synovitis and T-Cell Senescence
Ann. N.Y. Acad. Sci., December 1, 2005; 1062(1): 182 - 194.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Interv.Home page
A. P. Williams, A. R. Bateman, and S. I. Khakoo
HANGING IN THE BALANCE: KIR and Their Role in Disease
Mol. Interv., August 1, 2005; 5(4): 226 - 240.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Xu, A. N. Vallejo, Y. Jiang, C. M. Weyand, and J. J. Goronzy
Distinct Transcriptional Control Mechanisms of Killer Immunoglobulin-like Receptors in Natural Killer (NK) and in T Cells
J. Biol. Chem., June 24, 2005; 280(25): 24277 - 24285.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2004 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2004 by The American Association of Immunologists, Inc. All rights reserved.