Maintenance of the Body
T cell activation. For example, the CD4 and CD8 proteins that
distinguish the two major T cell groups are adhesion molecules
that help bind cells together during antigen recognition.
±e story isn’t over yet because step 2 comes next. Once antigen
binding has occurred, the T cell is stimulated but is still “idling,”
like a car that has been started but not put into gear. Before an
“idling” T cell can be “put into gear” and proliferate to form a
clone, it must also bind one or more
. ±ese signals are yet other molecules that
appear on the surfaces of APCs in tissues that are damaged or
invaded by pathogens. For example, dendritic cells and mac-
on their surfaces when the innate
defenses are being mobilized. ±e binding of B7 to its speciﬁc
receptor on a T cell is a crucial co-stimulatory signal.
What happens if a T cell binds to antigen without receiving
the co-stimulatory signal? In this case, the T cell becomes toler-
ant to that antigen and is unable to divide or secrete cytokines.
±is state of unresponsiveness to antigen is called
±e two-signal sequence acts as a kind of “double-handshake,”
a safeguard to prevent the immune system from destroying
healthy cells. Without this safeguard, class I MHC proteins, which
occur on all body cells and which display peptides from within
the cell, could activate cytotoxic T cells, leading to widespread
damage of healthy cells.
±e important thing to understand is that along with antigen
binding, co-stimulation is crucial for T cell activation. To go
back to our idling car analogy, the car will not go anywhere un-
less it has both (1) been started and (2) put into gear.
antigens—those that originate inside that cell. How do APCs ob-
tain endogenous antigens from another cell and display them on
class I MHCs in order to activate CD8 cells? Dendritic cells have
the special ability to do this. ±ey obtain other cells’ endogenous
antigens by either engulﬁng dying virus-infected or tumor cells,
or by importing antigens through temporary gap junctions with
infected cells. Dendritic cells then display these antigens on
class I and class II MHCs.
summarizes the roles that MHC proteins play in
T cell activation and function.
Activation and Differentiation of T Cells
T cell activation is actually a two-step process involving antigen
binding and co-stimulation. Both steps usually occur on the
surface of the same APC, and both steps are required for
±is ﬁrst step mostly entails what we have already described: T
cell antigen receptors
bind to an antigen-MHC complex
on the surface of an APC. Like B cell receptors, a TCR has vari-
able and constant regions, but it consists of two rather than four
As you will recall from our discussion of T cell education,
TCRs must perform
: ±ey must recognize
both MHC (self-antigen) and the foreign antigen it displays.
±e TCR that recognizes (by binding) the nonself-self complex
triggers multiple intracellular signaling pathways that lead to T
cell activation. Other T cell surface proteins also play a role in
Class I MHC
T cell receptor
T cell receptor
Role of MHC Proteins in Cellular Immunity
All nucleated cells
APCs (dendritic cells,
macrophages, B cells)
Naive CD8 cells and
cytotoxic T cells
Naive CD4 cells and
helper T cells
Foreign antigens on
pathogens or proteins
made by cancerous cells)*
Foreign antigens on
MHC send this message
If displayed by an APC:
“I belong to self, but have
captured a foreign invader. This is what it looks like. Kill
any cell that displays it.”
If displayed by any other body cell:
“I belong to self,
but have been invaded or become cancerous. Kill me!”
“I belong to self, but have captured a foreign invader.
This is what it looks like. Help me mount a defense
*Dendritic cells are an exception because they can present
endogenous antigens on their class I MHC proteins to activate CD8 cells.