There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
The adaptive immune response protects us from infection in a world of pathogens that
is forever evolving new variants. As the system is built on the generation of an open
repertoire of receptors, the recognition of self is unavoidable, and is guarded against
by deletion during lymphocyte development of those cells that are specific for ubiquitous
self antigens, and the silencing of those that are specific for self antigens only
encountered after cells achieve functional maturity in the periphery. This silencing
occurs when lymphocytes recognize antigens in the absence of suitable costimulatory
molecules. By contrast, when the same cell encounters the same ligand on a cell that
expresses costimulatory molecules, it will proliferate and differentiate into an effector
cell. These effector cells mediate protective immunity when the antigen is carried
by a pathogen, but they can mount autoimmune responses if the antigen is derived from
self. The major costimulatory molecules for CD4 T cells appear to be B7 and B7.2 that
bind to the CD28 and CTLA-4 receptors on the T cell. The signals from the TCR appear
to be integrated with those from the costimulator receptor, and the T cell response
depends on the precise nature of these signals, further conditioned by cytokines present
in the environment of the responding cell. B cells can be viewed in a similar way,
with the costimulatory molecule CD40 ligand and cytokines coming mainly from CD4 helper
T cells determining the fate of the responding B cell. The TCR is not simply an on
and off switch, since the precise way in which the TCR is ligated determines the differentiation
of the T cell and can alter the effector responses of established T cell lines. Thus,
the response capabilities of T cells are more flexible than originally believed, and
much of this flexibility comes from the interplay of TCR signals and signs from the
environment. If the biochemical nature of these differential signaling pathways were
known, it might be possible to develop simple pharmacological agents capable of diverting
T cell responses from harmful to innocuous by getting the T cell to reinterpret the
signals it is receiving via its receptors.(ABSTRACT TRUNCATED AT 400 WORDS)