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Cytotoxic T lymphocytes (CTL) can respond to a few viral peptide-MHC-I (pMHC-I) complexes among a myriad of virus-unrelated endogenous self pMHC-I complexes displayed on virus-infected cells. To elucidate the molecular recognition events on live CTL, we have utilized a self-assembled biosensor composed of semiconductor nanocrystals, quantum dots, carrying a controlled number of virus-derived (cognate) and other (noncognate) pMHC-I complexes and examined their recognition by antigen-specific T cell receptor (TCR) on anti-virus CD8(+) T cells. The unique architecture of nanoscale quantum dot/pMHC-I conjugates revealed that unexpectedly strong multivalent CD8-MHC-I interactions underlie the cooperative contribution of noncognate pMHC-I to the recognition of cognate pMHC-I by TCR to augment T cell responses. The cooperative, CD8-dependent spread of signal from a few productively engaged TCR to many other TCR can explain the remarkable ability of CTL to respond to virus-infected cells that present few cognate pMHC-I complexes.

Original publication




Journal article


Proc Natl Acad Sci U S A

Publication Date





16846 - 16851


Antigens, Viral, Autoantigens, Biosensing Techniques, CD8 Antigens, Clone Cells, HLA-A2 Antigen, Humans, In Vitro Techniques, Lymphocyte Activation, Models, Immunological, Quantum Dots, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Cytotoxic