Quantum dot/peptide-MHC biosensors reveal strong CD8-dependent cooperation between self and viral antigens that augment the T cell response.

Journal article

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.

Authors: Anikeeva, N; Lebedeva, T; Clapp, A; Goldman, E; Dustin, M

• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 103
• Issue: 45
• Pages: 16846-16851
• Publication date: 2006-11-01
• DOI: 10.1073/pnas.0607771103
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Lymphocyte Activation; Antigens, Viral; Biosensing Techniques; Antigens, CD8; Models, Immunological; Clone Cells; Autoantigens; Signal Transduction; Quantum Dots; Humans; HLA-A2 Antigen; Receptors, Antigen, T-Cell; T-Lymphocytes, Cytotoxic