Page 614 - Veterinary Immunology, 10th Edition

editing (Chapter 36). Although cell maturation stops when a T cell
VetBooks.ir leaves the thymus, its RAG genes remain active, and as a result,

V(D)J recombination continues. Consequently, the TCR genes
continue to diversify, and altered receptors are expressed on the cell

surface. This process is called receptor editing. If a cell successfully
edits its receptors, its maturation can proceed. Failure to do so will
result in its death. This is a potentially hazardous process since it
may permit the development of self-reactive T cells that have not

undergone selection within the thymus.

Peripheral T Cell Tolerance

Clonal Anergy

Low-affinity self-reactive T cells may survive the selection process

and leave the thymus. These must then be regulated by peripheral
tolerance mechanisms. One form of peripheral tolerance is clonal
anergy, the prolonged, antigen-specific suppression of T cell
function. Clonal anergy is triggered when T cells are exposed to
antigens in the absence of effective co-stimulation. T cells normally

require multiple co-stimulatory signals from several sources in
order to respond to antigen. If these signals are insufficient or
inappropriate, T cell responses will be suppressed and tolerance

results.
As pointed out in Chapter 14, binding of an antigen to a TCR is
by itself insufficient to trigger a T cell response. Indeed, occupation
of the TCR in the absence of co-stimulation causes tolerance. For
example, foreign protein solutions normally contain some

aggregated molecules. These aggregated molecules are readily
taken up and processed by dendritic cells and thus are highly
immunogenic. If a solution of such a protein, such as bovine γ-

globulin, is ultracentrifuged so that all the aggregates are removed,
then the aggregate-free solution will induce tolerance in mice due
to the absence of co-stimulation from antigen-presenting cells (Fig.
20.5).

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