Direct recognition of foreign MHC determinants by naive T cells mobilizes specific V beta families without skewing of the complementarity-determiningregion 3 length distribution

The capacity of T cells to interact with nonself-APC, also referred to as d irect allorecognition, is an essential feature of the cellular response inv olved in graft rejection. However, there is no study on TCR repertoire bias es associated with direct restricted T cell activation. In this paper, we h ave addressed the impact of direct recognition on the whole naive T cell re pertoire, using a new approach that provides, for the first time, an integr ated depiction of the quantitative and qualitative alterations in the TCR V beta transcriptome. This method can differentiate resting patterns from po lyclonally activated ones, as evidenced by superantigen usage. According to this new readout, we show that direct recognition of nonself-MHC molecules triggers mRNA accumulation of several TCR V beta families, specific to the combination studied. Moreover, in marked contrast to the situation that pr evails in indirect allorecognition, T cell activation through the direct pr esentation pathway was not associated with skewing of the complementarity d etermining region (CDR) 3 length distribution. Altogether, these data argue for the significance of TCR contacts with the MHC framework in direct allo recognition. In addition, the TCR diversity mobilized by this interaction a nd the massive TCR beta mRNA accumulation observed after a few days of cult ure suggest that a significant proportion of naive T cells receive a signal leading to TCR beta transcriptional activation even though only a few of t hem engage in mitosis.