Monomeric agonist peptide/MHCII complexes activate T-cells in an autonomous fashion

Authors:

René Platzer, Joschka Hellmeier, Janett Göhring, Iago Doel Perez, Philipp Schatzlmaier, Clara Bodner, Gerhard J. Schütz, Eva Sevcsik, Hannes Stockinger, Mario Brameshuber, Johannes B. Huppa

Keywords:

T-Cell activation

Abstract:

Molecular crowding of agonist peptide/MHC class II complexes (pMHCIIs) with structurally similar, yet per se non-stimulatory endogenous pMHCIIs has been postulated to sensitize T-cells for the recognition of single antigens on the surface of dendritic cells and B-cells. When testing this premise with the use of advanced live cell microscopy, we observed pMHCIIs as monomeric, randomly distributed entities diffusing rapidly after entering the APC surface. Synaptic TCR-engagement of highly abundant endogenous pMHCIIs was low or non-existent and affected neither TCR-engagement of rare agonist pMHCII in early and advanced synapses nor agonist-induced TCR-proximal signaling. Our findings highlight the capacity of single freely diffusing agonist pMHCIIs to elicit the full T-cell response in an autonomous and peptide-specific fashion with consequences for adaptive immunity and immunotherapeutic approaches.

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