DIFFERENCES IN THE LEVEL OF EXPRESSION OF CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX PROTEINS ON THYMIC EPITHELIAL AND DENDRITIC CELLS INFLUENCE THE DECISION OF IMMATURE THYMOCYTES BETWEEN POSITIVE AND NEGATIVE SELECTION

Both positive and negative selection of immature T cells rely on engag ement of their antigen-specific receptors (TCR) by peptide in associat ion with proteins encoded in the major histocompatibility complex (MHC ) protein. The decision made between these two outcomes seems to be de termined by the number of TCR engaged by peptide-MHC complexes. It has been unclear how such a mechanism can be reconciled with evidence tha t positive and negative selection occur in different thymic compartmen ts and are mediated by different antigen-presenting cells (APCs). In t his study we demonstrate that the level of class I MHC protein is 10-f old higher on thymic dendritic cells, which mediate the negative selec tion of immature T cells, than on thymic epithelial cells, which media te for positive selection. We also demonstrate that as little as a 3-f old increase in the level of a particular cognate peptide-MHC ligand i s sufficient to result in negative rather than positive selection. The results suggest that quantitative differences in the level of express ion of class I MHC proteins on thymic epithelial and dendritic cells c ontribute to the opposing roles these cells play in forming the repert oire of mature class I MHC restricted (CD8(+)) T cells.