International Immunology, Vol. 11, No. 3, 351-360,
March 1999
© 1999 Japanese Society for Immunology
Peptide dependency of alloreactive CD4+ T cell responses
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, 811 Rudolph Light Hall, Nashville, TN 37232, USA
Correspondence to: L. Van Kaer
Alloreactivity, the capacity of a large number of T lymphocytes to react with foreign MHC molecules, represents the cellular basis for the rejection of tissue grafts. Although it was originally assumed that the TCR of alloreactive T cells focus their recognition on the polymorphic residues that differ between the MHC molecules of responder and stimulator cells, studies in the MHC class I system have clearly demonstrated that MHC-bound peptides can influence this interaction. It remains unclear, however, whether peptides play an equally important role for the recognition of MHC class II molecules by alloreactive CD4+ T cells. Another issue that remains unresolved is the overall frequency of peptide-dependent versus peptide-independent alloreactive 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-Ab bound by a peptide (CLIP) derived from the class II-associated invariant chain. APC from these mice were used as targets and stimulators for alloreactive CD4+ T cells. Results demonstrated that the vast majority of CD4+ alloreactive T cells recognize MHC class II molecules in a peptide-dependent fashion.
Keywords: alloreactivity, gene-targeted mouse, H2-M, MHC class II molecules, peptides
1 Present address: GeneMedicine, The Woodlands, TX 77381, USA
2 Present address: Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA
Transmitting editor: E. Simpson
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