Comparative T cell receptor repertoire selection by antigen after adoptivetransfer: A glimpse at an antigen-specific preimmune repertoire

The low frequency of precursor cells specific for any particular antigen (A g) makes it difficult to characterize preimmune T cell receptor (TCR) reper toires and to understand repertoire selection during an immune response. We have undertaken a combined adoptive transfer single-cell PCR approach to p robe the Ag-specific preimmune repertoires of individual mice. Our strategy was to inject paired irradiated recipient mice with normal spleen cells pr epared from individual donors and to compare the TCR repertoires subsequent ly selected during a CD8 response to a defined model Ag. We found that alth ough some TCRs were shared, the TCR repertoires selected by mice receiving splenocytes from the same donor were not identical in terms of the TCRs sel ected and their relative frequencies. Our results together with computer si mulations imply that individual mice express distinct Ag-specific preimmune TCR repertoires composed of expanded clones and that selection by Ag is a random process.