Page 611 - Veterinary Immunology, 10th Edition

VetBooks.ir T Cell Tolerance

Central T Cell Tolerance

Negative Selection

Developing T cells must undergo education in the thymus where
they learn to discriminate between self and non–self-antigens.
Tolerance to self-antigens results when there are no functional T
cells that can bind self-antigens (Fig. 20.3). (It should be pointed out

that an exception must be made for MHC molecules. T cells must be
able to recognize them if they are to respond to foreign peptides.)
Although lymphocytes generate an enormous diversity of TCRs, far

fewer receptors are actually used by mature T cells than might be
anticipated. Several processes limit receptor diversity. First, the
mechanisms used to generate TCRs inevitably result in the
production of non-functional receptors. For example, two-thirds of
possible gene arrangements will be out of frame. Cells with these

non-functional TCRs die. As T cells mature within the thymus,
positive selection ensures that the cells that can bind self-antigens
survive. At this point, however, the cells whose receptors bind too

strongly to self-antigens also die (Fig. 20.4). The timing and extent
of this apoptosis depend on the affinity of the TCR for a self-
antigen. T cells that bind self-antigens strongly die earlier and more
completely than weakly binding cells. Thus the T cells that
eventually leave the thymus have been purged of dangerous, self-

reactive cells.

611