| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
Altered peptide ligands containing single amino acid substitutions have the potential to be used for modulating immune function. Using a panel of moth cytochrome c peptides, we demonstrate that different phases of naive CD4 T cell response are alternately modulated depending on altered peptide ligand dose and accessory molecule expression by APC. Weak agonists presented at high concentration, and with costimulation, efficiently induced early phase naive T cell activation as assessed by IL-2R/CD69 expression, but could only promote sufficient IL-2 for a short-lived proliferative response. In contrast, strong agonists and heteroclitic peptides induced early phase T cell activation even at low concentrations with costimulation, and allowed sustained IL-2 secretion and proliferation. In the absence of accessory molecule help, early and late phase activation was impaired with weak agonists, whereas strong agonists partially compensated for a lack of costimulation for early phase activation, and also promoted enhanced IL-2 with sustained proliferation. These studies support the hypothesis that the naive T cell response will be determined by the balance between provision of accessory molecule help and the affinity of peptide/MHC complexes for individual TCRs, and suggest that extended IL-2 production is the main facet of naive CD4 activation that is affected by altering the nature of the peptide.
This article has been cited by other articles:
|
|
 |
|
  S. Mostbock, S. Vidal, J. Schlom, and H. Sabzevari Enhanced Levels of Costimulation Lead to Reduced Effector/Memory CD8+ T Cell Functionality J. Immunol., September 15, 2007; 179(6): 3524 - 3534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. R. Reyes, S. Danese, M. Sans, C. Fiocchi, and A. D. Levine Redox Equilibrium in Mucosal T Cells Tunes the Intestinal TCR Signaling Threshold J. Immunol., August 15, 2005; 175(4): 2158 - 2166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Z. Mehal, S. Z. Sheikh, L. Gorelik, and R. A. Flavell TGF-{beta} signaling regulates CD8+ T cell responses to high- and low-affinity TCR interactions Int. Immunol., May 1, 2005; 17(5): 531 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Patke and D. L. Farber Modulation of Memory CD4 T Cell Function and Survival Potential by Altering the Strength of the Recall Stimulus J. Immunol., May 1, 2005; 174(9): 5433 - 5443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Zielinski, S. N. Jacob, F. Bouzahzah, B. E. Ehrlich, and J. Craft Naive CD4+ T Cells from Lupus-Prone Fas-Intact MRL Mice Display TCR-Mediated Hyperproliferation Due to Intrinsic Threshold Defects in Activation J. Immunol., April 15, 2005; 174(8): 5100 - 5109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bae, J. A. Martinson, and H. G. Klingemann Heteroclitic CD33 Peptide With Enhanced Anti-Acute Myeloid Leukemic Immunogenicity Clin. Cancer Res., October 15, 2004; 10(20): 7043 - 7052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Y. Choi and J. Craft Activation of Naive CD4+ T Cells In Vivo by a Self-Peptide Mimic: Mechanism of Tolerance Maintenance and Preservation of Immunity J. Immunol., June 15, 2004; 172(12): 7399 - 7407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. So, S. Salek-Ardakani, H. Nakano, C. F. Ware, and M. Croft TNF Receptor-Associated Factor 5 Limits the Induction of Th2 Immune Responses J. Immunol., April 1, 2004; 172(7): 4292 - 4297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Rigby, T. Rouse, and E. H. Field Total lymphoid irradiation nonmyeloablative preconditioning enriches for IL-4-producing CD4+-TNK cells and skews differentiation of immunocompetent donor CD4+ cells Blood, March 1, 2003; 101(5): 2024 - 2032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sasada, H. Yang, and E. L. Reinherz CD2 Facilitates Differentiation of CD4 Th Cells Without Affecting Th1/Th2 Polarization J. Immunol., February 1, 2002; 168(3): 1113 - 1122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Gebe, E. J. Novak, W. W. Kwok, A. G. Farr, G. T. Nepom, and J. H. Buckner T Cell Selection and Differential Activation on Structurally Related HLA-DR4 Ligands J. Immunol., September 15, 2001; 167(6): 3250 - 3256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Gerloni, S. Xiong, S. Mukerjee, S. P. Schoenberger, M. Croft, and M. Zanetti Functional cooperation between T helper cell determinants PNAS, November 2, 2000; (2000) 230429197. [Abstract] [Full Text]
|
|
|
|
|
|
D. M. Jelley-Gibbs, N. M. Lepak, M. Yen, and S. L. Swain Two Distinct Stages in the Transition from Naive CD4 T Cells to Effectors, Early Antigen-Dependent and Late Cytokine-Driven Expansion and Differentiation J. Immunol., November 1, 2000; 165(9): 5017 - 5026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Chung, V. P. Patel, M. Moran, L. A. Lewis, and M. C. Miceli Galectin-1 Induces Partial TCR {zeta}-Chain Phosphorylation and Antagonizes Processive TCR Signal Transduction J. Immunol., October 1, 2000; 165(7): 3722 - 3729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Huang, D. Tilly, A. Altman, K. Sugie, and H. M. Grey Inaugural Article: T-cell receptor antagonists induce Vav phosphorylation by selective activation of Fyn kinase PNAS, September 26, 2000; 97(20): 10923 - 10929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Colella, T. N.J. Bullock, L. B. Russell, D. W. Mullins, W. W. Overwijk, C. J. Luckey, R. A. Pierce, N. P. Restifo, and V. H. Engelhard Self-Tolerance to the Murine Homologue of a Tyrosinase-derived Melanoma Antigen: Implications for Tumor Immunotherapy J. Exp. Med., April 3, 2000; 191(7): 1221 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Rogers and M. Croft CD28, Ox-40, LFA-1, and CD4 Modulation of Th1/Th2 Differentiation Is Directly Dependent on the Dose of Antigen J. Immunol., March 15, 2000; 164(6): 2955 - 2963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Rogers, C. Dubey, and S. L. Swain Qualitative Changes Accompany Memory T Cell Generation: Faster, More Effective Responses at Lower Doses of Antigen J. Immunol., March 1, 2000; 164(5): 2338 - 2346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zivny, M. DeFronzo, W. Jarry, J. Jameson, J. Cruz, F. A. Ennis, and A. L. Rothman Partial Agonist Effect Influences the CTL Response to a Heterologous Dengue Virus Serotype J. Immunol., September 1, 1999; 163(5): 2754 - 2760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Rogers and M. Croft Peptide Dose, Affinity, and Time of Differentiation Can Contribute to the Th1/Th2 Cytokine Balance J. Immunol., August 1, 1999; 163(3): 1205 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. G. Saito, H.-C. Chang, and Y. Paterson Recognition of an MHC Class I-Restricted Antigenic Peptide Can Be Modulated by para-Substitution of Its Buried Tyrosine Residues in a TCR-Specific Manner J. Immunol., May 15, 1999; 162(10): 5998 - 6008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Rivoltini, P. Squarcina, D. J. Loftus, C. Castelli, P. Tarsini, A. Mazzocchi, F. Rini, V. Viggiano, F. Belli, and G. Parmiani A Superagonist Variant of Peptide MART1/Melan A27-35 Elicits Anti-Melanoma CD8+ T Cells with Enhanced Functional Characteristics: Implication for More Effective Immunotherapy Cancer Res., January 1, 1999; 59(2): 301 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Gramaglia, A. D. Weinberg, M. Lemon, and M. Croft Ox-40 Ligand: A Potent Costimulatory Molecule for Sustaining Primary CD4 T Cell Responses J. Immunol., December 15, 1998; 161(12): 6510 - 6517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Rogers, G. Huston, and S. L. Swain High Antigen Density and IL-2 Are Required for Generation of CD4 Effectors Secreting Th1 Rather Than Th0 Cytokines J. Immunol., October 15, 1998; 161(8): 3844 - 3852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wang, Y. Wang-Zhu, and H. Grey Interactions between double positive thymocytes and high affinity ligands presented by cortical epithelial cells generate double negative thymocytes with T cell regulatory activity PNAS, February 19, 2002; 99(4): 2181 - 2186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gerloni, S. Xiong, S. Mukerjee, S. P. Schoenberger, M. Croft, and M. Zanetti From the Cover: Functional cooperation between T helper cell determinants PNAS, November 21, 2000; 97(24): 13269 - 13274. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
