Inhibition of thymocyte positive selection by natural MHC: peptide ligands

The 3A9 transgenic mouse line carries the rearranged TCR genes from a T cell hybridoma that recognizes hen egg lysozyme peptide 46-61 in the context of MHC class II A(k) molecules. As expected, positive selection of immature 3A9 thymocytes to become mature CD4(+) 8(-) T cells was efficient on the "selecting" CBA (H-2(k)) genetic background but not on the "non-selecting" C57BL/6 (H-2(b)) background. Surprisingly, positive selection was also inefficient on the CBA x C57BL/6 F1 background (H-2(kb)). We present evidence that expression of A(beta)(b) molecules on thymus epithelium (in conjunction with A(alpha)(b) or A(u)(k) molecules) inhibits the positive selection of 3A9 thymocytes mediated by A(alpha)(k):A(beta)(k) complexes, in a process evocative of peptide antagonism of mature T cells.