Receptor revision in peripheral T cells creates a diverse V beta repertoire

In V beta5 transgenic mice, the age-dependent accumulation of V beta5-CD4() T cells expressing endogenous VP elements represents an exception to the rule of strict allelic exclusion at the TCR beta locus. The appearance of t hese cells is limited to the lymphoid periphery and is driven by a peripher ally expressed tolerogen, Expression of the lymphoid-specific components of the recombinase machinery and the presence of recombination intermediates strongly suggest that TCR revision rescues tolerogen-reactive peripheral T cells from deletion. Here, we report that the appearance of V beta5-CD4(+) T cells is CD28-dependent. In addition, we find that the TCR repertoire of this unusual population of T cells in individual V beta5 transgenic mice is surprisingly diverse, both at the level of surface protein and at the nucl eotide level within a given family of V(D)J beta rearrangements. This faith ful recreation of the nontransgenic repertoire suggests that endogenous V b eta -expressing populations do not arise front expansion of an initially ra re subset, Furthermore, the undersized N regions in revised TCR genes disti nguish these sequences from those generated in the adult thymus, The divers ity of the revised TCRs, the minimal mouse-to-mouse variation in the expres sed endogenous V beta repertoire, the atypical length of junctional sequenc es, and the CD28 dependence of the accumulation of V beta5(-)CD4(+) T cells all point to their extrathymic origin. Thus, tolerogen-driven receptor rev ision in peripheral T cells can expand the TCR repertoire extrathymically, thereby contributing to the flexibility of the immune repertoire.