CONTRAST BETWEEN CLASS-I AND CLASS-II MHC-MEDIATED DIFFERENTIATION OF A CD4(+)CD8(+) T-CELL LINE - IMPLICATIONS FOR LINEAGE COMMITMENT

Experiments in transgenic mice have demonstrated that thymocyte differentiation into the mature CD4(+) helper or CD8(+) cytotoxic T cell lineages is ultimately dependent upon the specificity of the TCR for class II or class 1 MHC molecules respectively. However, the initial mechanistic events involved in this process remain unclear. To address this issue, we have expressed a TCR specific for an ovalbumin peptide and the K-b class I MHC molecule in the DPK CD4(+)CD8(+) precursor T cell line. This cell line originally expressed a TCR specific for a pigeon cytochrome c peptide and class II MHC molecules and has been shown previously to differentiate into CD4(+)CD8(-) cells upon recognition of antigen in vitro or thymic epithelial cells in vivo. Surprisingly, we find that recognition of either class I or class II MHC by these cells initiates differentiation into the CD4(+) lineage and induces down-regulation of recombination associated genes. Unlike recognition of class II MHC, however, recognition of class I MHC does not induce full maturation. These results support a model in which (i) commitment to the CD4 lineage occurs prior to positive selection and (ii) CD4 lineage commitment is associated with a requirement for activation by a class II MHC-specific TCR in order to complete differentiation.