Page 407 - Veterinary Immunology, 10th Edition

VetBooks.ir Overall Considerations

T cells are highly mobile cells. As described in Chapter 12, they
migrate rapidly through lymph nodes while continuously scanning

the surfaces of dendritic cells for antigens. When it recognizes a
foreign antigen, a T cell changes its behavior. It slows down, stops,
and eventually binds strongly to the antigen-presenting cell and
forms a synapse. Whether or not a T cell stops depends on how
strongly it binds to the target antigen. It will not stop for weakly

binding antigens.
Once the synapse forms, TCRs and co-stimulatory molecules
signal to the T cell. However, the TCR does not function simply as

an on/off switch. Instead, differences in the strength of binding, in
the amount of co-stimulation, and in the duration of the cell
interaction affect T cell responses.
Because MHC molecules can bind many different antigenic
peptides, any individual peptide will only be displayed in small

amounts. T cells must be able to recognize these few specific
peptide-MHC complexes among a vast excess of MHC molecules
carrying irrelevant peptides. The number of MHC-peptide

complexes signaling to the T cell is also important since the
stimulus needed to trigger a T cell response varies. For example,
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only one MHC-peptide complex is needed to trigger a CD8 T cell
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response. At least 8000 TCRs must bind antigen for a CD4 T cell to
become activated in the absence of CD28, but only about 1000 TCRs

need be engaged if CD28 is present (Fig. 14.11). The duration of
signaling also determines a T cell's response. In the presence of
appropriate antigens, T cells need to bind DCs for less than 15

seconds before pulling away. T cells can make 30 to 40 APC
contacts within a minute. Sustained signaling is, however, required
for maximal T cell activation and is maintained by serial triggering
of its TCRs. Thus during the prolonged cell interaction process,
each MHC-peptide complex may trigger up to 200 TCRs. This serial

triggering depends on the kinetics of TCR-ligand interaction. CD28,
for example, reduces the time needed to trigger a T cell and lowers
the threshold for TCR triggering. Adhesion molecules stabilize the

binding of T cells to antigen-processing cells and allow the signal to

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