Generation of T Cell Diversity

T cell gene rearrangement takes place in the thymus. The mechanism used to generate T cell diversity is essentially the same as that used for the generation of B cell diversity but without the somatic hypermutation on activation.

 

The T cell receptor is made up of α and β chains. The α chain is coded for by a set of V gene segments (Vα) and a set of joining or J gene segments (Jα). The β chain variable domain is coded for by a set of V gene segments (Vβ), a set of diversity or D gene segments (Dβ) and a set of J gene segments (Jβ).

 

The somatic recombination process of the α chain involves the random selection of a Vα gene segment which is then joined to a randomly selected Jα gene segment. This is catalysed by recombination activation genes (RAGs). Vα genes are prevented from accidentally joining to other Vα gene segments by the use of recombination signalling sequences (RSS) which consist of a heptamer, a 12 or 23 nucleotide spacer and a nonamer. This is the 12/23 rule and it prevents gene segments with a 12 nucleotide spacer being joined to other 12 spacer segments and gene segments with a 23 nucleotide spacer being joined to other 23 spacer segments. This same process prevents J, D and Vβ gene segments from self joining. The joining process is not precise and introduces further Junctional diversification.

 

The variable β chain is created by a randomly selected Dβ gene segment joining to a randomly selected Jβ segment and then the combination joining to a randomly selected Vβ gene segment. Junctional diversity also is introduced during these joins.

 

Diversity is concentrated in the CDR3 loop, contributed to by the joining of the β chain DJ gene segments.

 


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