Increased mobility of major histocompatibility complex I-peptide complexes decreases the sensitivity of antigen recognition.
CD8(+) cytotoxic T lymphocytes (CTL) can recognize and kill target cells expressing only a few cognate major histocompatibility complex (MHC) I-peptide complexes. This high sensitivity requires efficient scanning of a vast number of highly diverse MHC I-peptide complexes by the T cell receptor in the contact site of transient conjugates formed mainly by nonspecific interactions of ICAM-1 and LFA-1. Tracking of single H-2K(d) molecules loaded with fluorescent peptides on target cells and nascent conjugates with CTL showed dynamic transitions between states of free diffusion and immobility. The immobilizations were explained by association of MHC I-peptide complexes with ICAM-1 and strongly increased their local concentration in cell adhesion sites and hence their scanning by T cell receptor. In nascent immunological synapses cognate complexes became immobile, whereas noncognate ones diffused out again. Interfering with this mobility modulation-based concentration and sorting of MHC I-peptide complexes strongly impaired the sensitivity of antigen recognition by CTL, demonstrating that it constitutes a new basic aspect of antigen presentation by MHC I molecules.
Segura
Jean-Manuel
JM
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, CH-1066 Epalinges, Switzerland.
Guillaume
Philippe
P
Mark
Silke
S
Dojcinovic
Danijel
D
Johannsen
Alexandre
A
Bosshard
Giovanna
G
Angelov
Georgi
G
Legler
Daniel F
DF
Vogel
Horst
H
Luescher
Immanuel F
IF
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D007739:L Cells; D051379:Mice; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1