For an efficient immune response, receptors on T cells must interact with peptide–major histocompatibility complex (pMHC) of antigen-presenting cells (APC) to form 'immune synapses', but the role of other peptides in these aggregations remains unclear. In December 3 on line Nature Immunology, Christoph Wülfing and colleagues from Stanford University show that to achieve the strongest response, completely unrelated fragments of protein — normally from the host itself — must also be carried into the immune synapses.

Wülfing et al. used video microscopy and directly observed that a peptide on APC that lacks most major T cell contact residues can nonetheless accumulate in T cell–induced synapses in the presence of agonist peptide–major histocompatibility complex and enhance T cell activation (Nat Immunol 2001, DOI: 10.1038/ni741).

"These data indicate that endogenous peptides that have no in vitro biological activity alone can accumulate and function in critical signaling structures as an...

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