A molecular chart of thymocyte positive selection

As a new slant on T lymphocyte repertoire selection, we have examined batte ries of TCR sequences in thymi from transgenic, mice engineered to exhibit limited, focussed TCR diversity. We have tracked the fate of differentiatin g thymocytes expressing a set of particular TCR through the positive select ion process. Subtly different TCR sequences can promote different maturatio n pathways and commitment choices. Two distinct routes are followed by CD8- lineage cells interacting with MHC class I molecules, via TCRhi CD4(+)CD8() or CD4(+)CD8(int) intermediates, while CD4-lineage cells mature exclusive ly via a CD4(+)CD8(int) stage. The CD8-lineage routes are partially exclusi ve, indicating that the latter cell type is not always preceded by the form er. The distribution of sequences also indicates that CD4/CD8-lineage commi tment is not strictly correlated with the class of MHC molecule engaged, an d that some mechanism prevents mismatched intermediates from achieving full maturity.