T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation.
After homing to lymph nodes, CD8+ T cells are primed by dendritic cells (DCs) in three phases. During phase one, T cells undergo brief serial contacts with DCs for several hours, whereas phase two is characterized by stable T cell-DC interactions. We show here that the duration of phase one and T cell activation kinetics correlated inversely with the number of complexes of cognate peptide and major histocompatibility complex (pMHC) per DC and with the density of antigen-presenting DCs per lymph node. Very few pMHC complexes were necessary for the induction of full-fledged T cell activation and effector differentiation. However, neither T cell activation nor transition to phase two occurred below a threshold antigen dose determined in part by pMHC stability. Thus, phase one permits T cells to make integrated 'measurements' of antigen dose that determine subsequent T cell participation in immune responses.
Henrickson
Sarah E
SE
Department of Pathology and the Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mempel
Thorsten R
TR
Mazo
Irina B
IB
Liu
Bai
B
Artyomov
Maxim N
MN
Zheng
Huan
H
Peixoto
Antonio
A
Flynn
Michael P
MP
Senman
Balimkiz
B
Junt
Tobias
T
Wong
Hing C
HC
Chakraborty
Arup K
AK
von Andrian
Ulrich H
UH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000954:Antigens, Surface; D010446:Peptide Fragments