ANTAGONIST PEPTIDE SELECTS THYMOCYTES EXPRESSING A CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-RESTRICTED T-CELL RECEPTOR INTO THE CD8 LINEAGE

CD4/CD8 lineage decision is an important event during T cell maturatio n in the thymus. CD8 T cell differentiation usually requires corecogni tion of major histocompatibility complex (MHC) class I by the T cell r eceptor (TCR) and CD8, whereas CD4 T cells differentiate as a conseque nce of MHC class IT recognition by the TCR and CD4. The involvement of specific peptides in the selection of T cells expressing a particular TCR could be demonstrated so far for the CD8 lineage only. We used mi ce transgenic for an MHC class II-restricted TCR to investigate the ro le of antagonistic peptides in CD4 T cell differentiation. Interesting ly, antagonists blocked the development of CD4(+) cells that normally differentiate in thymus organ culture from those mice, and they induce d the generation of CD8(+) cells in thymus organ culture from mice imp aired in CD4+ cell development (invariant chain-deficient mice). These results are in line with recent observations that antagonistic signal s direct differentiation into the CD8 lineage, regardless of MHC speci ficity.