Size estimate of the αβ TCR repertoire of naive mouse splenocytes

The diversity of the T cell repertoire of mature T splenocytes is generated, in the thymus, by pairing of alpha and beta variable domains of the cup TCR and by the rearrangements of various gene segments encoding these domains. In the periphery, it results from competition between various T cell subpopulations including recent thymic migrants and long-lived T cells, Quantitative data on the actual size of the T cell repertoire are lacking. Using PCR methods and extensive sequencing, we have measured for the first time the size of the TCR-alpha beta repertoire of naive mouse T splenocytes, There are 5-8 x 10(5) different nucleotide sequences of BV chains in the whole spleen of young adult mice. We have also determined the size of the alpha beta repertoire in a subpopulation of AV2(+) T splenocytes, which allows us to provide a minimum estimate of the cup repertoire. We find that the mouse spleen harbors about 2 x 10(6) clones of about 10 cells each. This figure, although orders of magnitude smaller than the maximum theoretical diversity (estimated up to 10(15)), is still large enough to maintain a high functional diversity.