CD4(-CELLS MATURE IN THE ABSENCE OF MHC CLASS-I AND CLASS-II EXPRESSION IN LY-6A.2 TRANSGENIC MICE() T)

The TCRs expressed on T lymphocytes recognize foreign peptides bound t o MHC molecules, This reactivity is the basis of specific immune respo nse to the foreign Ag, How such specificities are generated in the thy mus is still being debated. Signals generated through TCR upon interac tion with self MHC-peptide complexes are critical for maturation of th e CD4(+) helper and CD8(+) cytotoxic subsets. We have observed maturat ion of CD4(+) but not CD8(+) T cells in Ly-6A.2 transgenic MHC null mi ce. Since there can be no interactions with MHC molecules in these mic e, these CD4(+) cells must express the T cell repertoire that exists b efore positive and negative selection, Interestingly, despite an absen ce of selection by MHC molecules, the CD4+ cells that mature recognize MHC molecules at a frequency as high as in CD4(+) cells in normal mic e, These results demonstrate that: 1) the germline sequences encoding TCRs are biased toward reactivity to MHC molecules; and 2) CD4(+) cell s as opposed to CD8(+) cells have distinct lineage commitment signals. These results also suggest that signals originating from Ly-6 can pro mote or substitute for signals generated from TCR that are required fo r positive selection. Moreover, this animal model offers a system to s tudy T cell development in the thymus that can provide insights into m echanisms of lineage commitment in developing T cells.