Page 540 - Veterinary Immunology, 10th Edition

Looping out and deletion account for more than 75% of TCR
VetBooks.ir rearrangements. The rest of the rearrangements are due to either

unequal sister chromatid exchange or inversion. That is, moving an
inverted segment of gene into a position beside a segment in the

opposite orientation.

Base Insertion and Deletion

Although, in general, TCRs are constructed from a smaller V-, D-,
and J-gene pool than immunoglobulins, their diversity is greater as
a result of junctional diversity (Box 17.2). Random N-nucleotides

may be inserted at the V, D, and J junctions using TdT. Up to five
nucleotides may be added between V and D and four between D
and J genes. Likewise, random nucleotides may be removed by

nucleases. This insertion of N-nucleotides and base deletion is
probably the most significant component of TCR junctional
diversity.

Box 17.2

Methods of Generating TCR Diversity

VJ, VJJ, VDJ, and VDDJ gene recombination

Base deletion

Base insertion

Combinatorial association

Somatic Mutation

Somatic mutation does not occur in TCR V genes. Although T cells
must be able to recognize a foreign antigen in association with the

presenting major histocompatibility complex (MHC) molecule, it is
essential that they do not respond to self-antigens. If random
somatic mutation were to occur, it would carry the unacceptable
risk of altering MHC restriction and rendering the foreign antigen

unrecognizable. It might also lead to the production of TCRs able to
bind self-antigens and thus trigger autoimmunity.

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