| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
To futher our understanding of the mechanisms underlying the
diverse effects of altered peptide ligands (APL) on T cell activation,
we used a population of nonactivated spleen cells from mice that
expressed a transgenic TCR specific for myelin basic protein Ac1-11 and
peptide analogues that display either enhanced or decreased affinities
for TCR/MHC to address the question whether APL-induced signaling
through the TCR can regulate the capability of APC to activate T cells.
We demonstrate that weak agonists APL are poor inducers of all aspects
of the activation of both the responder T cells and the APC.
Enhancement of the antigenic signal by augmenting the binding of the
weak agonists to MHC reversed their defective activating capacity.
Enhancement of costimulation by engagement of CD28 only resulted in
augmentation of the capacity of the weak agonist APL to induce
proliferation and IL-2/IL-3 production, but not CD40L or IL-12Rß2
chain expression on T cells, CD80/CD86 expression on APC, IL-12
secretion, or IFN-
production. Exogenous IL-12 promoted IFN-
production in the presence of the weak agonists. These studies
demonstrate that there is a critical threshold of antigenic signal
required for full activation of the T cell-APC interactions needed for
the differentiation of Th1 cells. The provision of excess costimulation
can overcome some of the defects in T cell activation by weak agonists,
but is insufficient to induce a sufficient level of CD40L expression
needed for engagement of CD40 on APC with subsequent IL-12 production
and induction of IL-12Rß2 chain expression.
This article has been cited by other articles:
|
|
 |
|
  K. M. Pollard, M. Arnush, P. Hultman, and D. H. Kono Costimulation Requirements of Induced Murine Systemic Autoimmune Disease J. Immunol., November 1, 2004; 173(9): 5880 - 5887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Murphy, J. Yu, Q. Jiao, M. Lin, T. Chitnis, and M. H. Sayegh A Novel Mechanism for the Immunomodulatory Functions of Class II MHC-Derived Peptides J. Am. Soc. Nephrol., April 1, 2003; 14(4): 1053 - 1065. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Ahlers, I. M. Belyakov, S. Matsui, and J. A. Berzofsky Signals delivered through TCR instruct IL-12 receptor (IL-12R) expression: IL-12 and tumor necrosis factor-{alpha} synergize for IL-12R expression at low antigen dose Int. Immunol., November 1, 2001; 13(11): 1433 - 1442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Horwood, J. Elliott, T. J. Martin, and M. T. Gillespie IL-12 Alone and in Synergy with IL-18 Inhibits Osteoclast Formation In Vitro J. Immunol., April 15, 2001; 166(8): 4915 - 4921. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
