Functional CD8+ but not CD4+ T cell responses develop independent of thymic epithelial MHC

The role of nonthymic epithelial (non-TE) MIHC in T cell repertoire selection remains controversial. To analyze the relative roles of thymic epithelial (TE) and non-TE MHC in T cell repertoire selection, we have generated tetraparental aggregation chimeras (B6-nude <-> BALB/c and B6 <-> BALB/c-nude) harboring T and B cells from both parents, whereas TIE cells originated exclusively from the non-nude donor. These chimeras mounted protective virus-specific TE and non-TE MHC-restricted T cell responses. To further evaluate whether non-TE MIHC alone was sufficient to generate a functional T cell repertoire, we generated tetraparental aggregation chimeras lacking MHC class II (B6-nude <-> MHCII-/-) or both MHC molecules (B6-nude <-> MHCl-/-II-/-) on TE cells, but not on cells of B6-nude origin. Chimeras with MHC-deficient TE cells mounted functional virus-specific CD8(+) but not CD4(+) T cell responses. Thus, maturation of functional CD4(+) T cell responses required MIHC class II on thymic epithelium, whereas CD8(+) T cells matured in the absence of TE MHC.