Quantum dot/peptide-MHC biosensors reveal strong CD8-dependent cooperation between self and viral antigens that augment the T cell response.
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.
Anikeeva
Nadia
N
Department of Microbiology and Immunology and Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Lebedeva
Tatiana
T
Clapp
Aaron R
AR
Goldman
Ellen R
ER
Dustin
Michael L
ML
Mattoussi
Hedi
H
Sykulev
Yuri
Y
D000956:Antigens, Viral; D001324:Autoantigens; D015374:Biosensing Techniques; D016827:CD8 Antigens / Q000378:metabolism*; D002999:Clone Cells; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D018448:Models, Immunological; D045663:Quantum Dots; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D001324:Autoantigens; D016827:CD8 Antigens; D015789:HLA-A2 Antigen; D011948:Receptors, Antigen, T-Cell