| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Microbiology and Immunology and
Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599
Most current models of T cell activation postulate a requirement
for two distinct signals. One signal is delivered through the TCR by
engagement with peptide/MHC complexes, and the second is delivered by
interaction between costimulatory molecules such as CD28 and its
ligands CD80 and CD86. Soluble peptide/MHC tetramers provide an
opportunity to test whether naive CD8+ T cells can be
activated via the signal generated through the TCR-
ß in the
absence of any potential costimulatory molecules. Using T cells from
two different TCR transgenic mice in vitro, we find that TCR engagement
by peptide/MHC tetramers is sufficient for the activation of naive
CD8+ T cells. Furthermore, these T cells proliferate,
produce cytokines, and differentiate into cytolytic effectors. Under
the conditions where anti-CD28 is able to enhance proliferation of
normal B6 CD4+, CD8+, and TCR transgenic
CD8+ T cells with anti-CD3, we see no effect of
anti-CD28 on proliferation induced by tetramers. The results of
this experiment argue that given a strong signal delivered through the
TCR by an authentic ligand, no costimulation is
required.
This article has been cited by other articles:
|
|
 |
|
  S. Tian, R. Maile, E. J. Collins, and J. A. Frelinger CD8+ T Cell Activation Is Governed by TCR-Peptide/MHC Affinity, Not Dissociation Rate J. Immunol., September 1, 2007; 179(5): 2952 - 2960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Hess, C. Barnes, M. D. Woolard, M. D. L. Johnson, J. M. Cullen, E. J. Collins, and J. A. Frelinger Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin Blood, April 15, 2007; 109(8): 3300 - 3307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Woolard, J. E. Wilson, L. L. Hensley, L. A. Jania, T. H. Kawula, J. R. Drake, and J. A. Frelinger Francisella tularensis-Infected Macrophages Release Prostaglandin E2 that Blocks T Cell Proliferation and Promotes a Th2-Like Response J. Immunol., February 15, 2007; 178(4): 2065 - 2074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Martin-Orozco, Y.-H. Wang, H. Yagita, and C. Dong Cutting Edge: Programed Death (PD) Ligand-1/PD-1 Interaction Is Required for CD8+ T Cell Tolerance to Tissue Antigens J. Immunol., December 15, 2006; 177(12): 8291 - 8295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Cesson, K. Stirnemann, B. Robert, I. Luescher, T. Filleron, G. Corradin, J.-P. Mach, and A. Donda Active Antiviral T-Lymphocyte Response Can Be Redirected against Tumor Cells by Antitumor Antibody x MHC/Viral Peptide Conjugates Clin. Cancer Res., December 15, 2006; 12(24): 7422 - 7430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Maile, C. M. Barnes, A. I. Nielsen, A. A. Meyer, J. A. Frelinger, and B. A. Cairns Lymphopenia-Induced Homeostatic Proliferation of CD8+ T Cells Is a Mechanism for Effective Allogeneic Skin Graft Rejection following Burn Injury. J. Immunol., June 1, 2006; 176(11): 6717 - 6726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Klein and I. N. Crispe Complete differentiation of CD8+ T cells activated locally within the transplanted liver J. Exp. Med., February 21, 2006; 203(2): 437 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Maile, C. A. Siler, S. E. Kerry, K. E. Midkiff, E. J. Collins, and J. A. Frelinger Peripheral "CD8 Tuning" Dynamically Modulates the Size and Responsiveness of an Antigen-Specific T Cell Pool In Vivo J. Immunol., January 15, 2005; 174(2): 619 - 627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lev, R. Noy, K. Oved, H. Novak, D. Segal, P. Walden, D. Zehn, and Y. Reiter Tumor-specific Ab-mediated targeting of MHC-peptide complexes induces regression of human tumor xenografts in vivo PNAS, June 15, 2004; 101(24): 9051 - 9056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Kerry, J. Buslepp, L. A. Cramer, R. Maile, L. L. Hensley, A. I. Nielsen, P. Kavathas, B. J. Vilen, E. J. Collins, and J. A. Frelinger Interplay between TCR Affinity and Necessity of Coreceptor Ligation: High-Affinity Peptide-MHC/TCR Interaction Overcomes Lack of CD8 Engagement J. Immunol., November 1, 2003; 171(9): 4493 - 4503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Vacchio and R. J. Hodes CD28 Costimulation Is Required for In Vivo Induction of Peripheral Tolerance in CD8 T Cells J. Exp. Med., January 6, 2003; 197(1): 19 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Buslepp, S. E. Kerry, D. Loftus, J. A. Frelinger, E. Appella, and E. J. Collins High Affinity Xenoreactive TCR:MHC Interaction Recruits CD8 in Absence of Binding to MHC J. Immunol., January 1, 2003; 170(1): 373 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Kovacs, M. V. Maus, J. L. Riley, G. S. Derimanov, G. A. Koretzky, C. H. June, and T. H. Finkel Human CD8+ T cells do not require the polarization of lipid rafts for activation and proliferation PNAS, November 12, 2002; 99(23): 15006 - 15011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Schott, N. Bertho, Q. Ge, M. M. Maurice, and H. L. Ploegh Class I negative CD8 T cells reveal the confounding role of peptide-transfer onto CD8 T cells stimulated with soluble H2-Kb molecules PNAS, October 15, 2002; 99(21): 13735 - 13740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lev, H. Novak, D. Segal, and Y. Reiter Recruitment of CTL Activity by Tumor-Specific Antibody-Mediated Targeting of Single-Chain Class I MHC-Peptide Complexes J. Immunol., September 15, 2002; 169(6): 2988 - 2996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Wang, A. Sharma, R. Maile, M. Saad, E. J. Collins, and J. A. Frelinger Peptidic Termini Play a Significant Role in TCR Recognition J. Immunol., September 15, 2002; 169(6): 3137 - 3145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Demirci, W. Gao, X. X. Zheng, T. R. Malek, T. B. Strom, and X. C. Li On CD28/CD40 Ligand Costimulation, Common {gamma}-Chain Signals, and the Alloimmune Response J. Immunol., May 1, 2002; 168(9): 4382 - 4390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Y. Kim and H.-S. Teh TNF Type 2 Receptor (p75) Lowers the Threshold of T Cell Activation J. Immunol., December 15, 2001; 167(12): 6812 - 6820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hombach, A. Wieczarkowiecz, T. Marquardt, C. Heuser, L. Usai, C. Pohl, B. Seliger, and H. Abken Tumor-Specific T Cell Activation by Recombinant Immunoreceptors: CD3{zeta} Signaling and CD28 Costimulation Are Simultaneously Required for Efficient IL-2 Secretion and Can Be Integrated Into One Combined CD28/CD3{zeta} Signaling Receptor Molecule J. Immunol., December 1, 2001; 167(11): 6123 - 6131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-W. Mittrucker, M. Kursar, A. Kohler, R. Hurwitz, and S. H. E. Kaufmann Role of CD28 for the Generation and Expansion of Antigen-Specific CD8+ T Lymphocytes During Infection with Listeria monocytogenes J. Immunol., November 15, 2001; 167(10): 5620 - 5627. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. M. Padigel, P. J. Perrin, and J. P. Farrell The Development of a Th1-Type Response and Resistance to Leishmania major Infection in the Absence of CD40-CD40L Costimulation J. Immunol., November 15, 2001; 167(10): 5874 - 5879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Y. Tsang, M. Zhu, J. Even, J. Gulley, P. Arlen, and J. Schlom The Infection of Human Dendritic Cells with Recombinant Avipox Vectors Expressing a Costimulatory Molecule Transgene (CD80) to Enhance the Activation of Antigen-specific Cytolytic T Cells Cancer Res., October 1, 2001; 61(20): 7568 - 7576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Maile, B. Wang, W. Schooler, A. Meyer, E. J. Collins, and J. A. Frelinger Antigen-Specific Modulation of an Immune Response by In Vivo Administration of Soluble MHC Class I Tetramers J. Immunol., October 1, 2001; 167(7): 3708 - 3714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Piccirillo and E. M. Shevach Cutting Edge: Control of CD8+ T Cell Activation by CD4+CD25+ Immunoregulatory Cells J. Immunol., August 1, 2001; 167(3): 1137 - 1140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Wang, C. C. Norbury, R. Greenwood, J. R. Bennink, J. W. Yewdell, and J. A. Frelinger Multiple Paths for Activation of Naive CD8+ T Cells: CD4-Independent Help J. Immunol., August 1, 2001; 167(3): 1283 - 1289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hombach, D. Sent, C. Schneider, C. Heuser, D. Koch, C. Pohl, B. Seliger, and H. Abken T-Cell Activation by Recombinant Receptors: CD28 Costimulation Is Required for Interleukin 2 Secretion and Receptor-mediated T-Cell Proliferation but Does Not Affect Receptor-mediated Target Cell Lysis Cancer Res., March 1, 2001; 61(5): 1976 - 1982. [Abstract] [Full Text]
|
|
|
|
|
|
H. Ito, J. Kurtz, J. Shaffer, and M. Sykes CD4 T Cell-Mediated Alloresistance to Fully MHC-Mismatched Allogeneic Bone Marrow Engraftment Is Dependent on CD40-CD40 Ligand Interactions, and Lasting T Cell Tolerance Is Induced by Bone Marrow Transplantation with Initial Blockade of this Pathway J. Immunol., March 1, 2001; 166(5): 2970 - 2981. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Grayson, K. Murali-Krishna, J. D. Altman, and R. Ahmed Gene Expression in Antigen-Specific CD8+ T Cells During Viral Infection J. Immunol., January 15, 2001; 166(2): 795 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Williams, J. Trambley, J. Ha, A. B. Adams, M. M. Durham, P. Rees, S. R. Cowan, T. C. Pearson, and C. P. Larsen Genetic Characterization of Strain Differences in the Ability to Mediate CD40/CD28-Independent Rejection of Skin Allografts J. Immunol., December 15, 2000; 165(12): 6849 - 6857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-G. Lim, K. Bieganowska Bourcier, G. J. Freeman, and D. A. Hafler Examination of CD8+ T Cell Function in Humans Using MHC Class I Tetramers: Similar Cytotoxicity but Variable Proliferation and Cytokine Production Among Different Clonal CD8+ T Cells Specific to a Single Viral Epitope J. Immunol., December 1, 2000; 165(11): 6214 - 6220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhan, A. J. Corbett, J. L. Brady, R. M. Sutherland, and A. M. Lew CD4 Help-Independent Induction of Cytotoxic CD8 Cells to Allogeneic P815 Tumor Cells Is Absolutely Dependent on Costimulation J. Immunol., October 1, 2000; 165(7): 3612 - 3619. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
