Peptide dependency of alloreactive CD4(+) T cell responses

Alloreactivity, the capacity of a large number of T lymphocytes to react wi th foreign MHC molecules, represents the cellular basis for the rejection o f tissue grafts. Although it was originally assumed that the TCR of allorea ctive T cells focus their recognition on the polymorphic residues that diff er between the MHC molecules of responder and stimulator cells, studies in the MHC class I system have clearly demonstrated that MHC-bound peptides ca n influence this interaction. It remains unclear, however, whether peptides play an equally important role for the recognition of MHC class II molecul es by alloreactive CD4(+) T cells. Another issue that remains unresolved is the overall frequency of peptide-dependent versus peptide-independent allo reactive T cells. We have addressed these questions with antigen-presenting cells (APC) from H2-M mutant mice that predominantly express a single MHC class Ii-peptide complex, H2-A(b) bound by a peptide (CLIP) derived from th e class Ii-associated invariant chain. APC from these mice were used as tar gets and stimulators for alloreactive CD4(+) T cells. Results demonstrated that the vast majority of CD4(+) alloreactive T cells recognize MHC class I I molecules in a peptide-dependent fashion.