A functional role for signal transduction via the cytoplasmic domains of MHC class II proteins.
B cell transfectants expressing MHC class II (Ia) molecules with truncated cytoplasmic domains are defective in both antigen presentation and in anti-Ia induced intracellular signaling. In this report we show that the Ag presentation defect in a truncated-Ia expressing transfectant can be overcome by providing the second messenger for the Ia-mediated signaling event. Preincubation with dibutyryl-cAMP restored the ability of the truncated Ia expressing-transfectant to stimulate IL-2 release by otherwise nonresponsive T hybrids. This provides direct functional evidence that signaling via the cytoplasmic domains of MHC class II proteins leads to the generation of accessory signals in the B cell that are important in T cell activation. The dibutyryl-cAMP induced signal must be on the same cell as the restricting element, does not bypass the requirement for occupancy of the T cell receptor with its normal ligand, and is lost upon fixation of the cells. Thus T cell-B cell interaction involves a two way communication in which both cells sense and respond to the formation of the antigen/MHC/TCR complex.
St-Pierre
Y
Y
Department of Immunology, University of Toronto, Ontario, Canada.
Nabavi
N
N
Ghogawala
Z
Z
Glimcher
L H
LH
Watts
T H
TH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D003593:Cytoplasm / Q000276:immunology* / Q000502:physiology; D000939:Epitopes / Q000276:immunology; D005404:Fixatives; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000276:immunology; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D000939:Epitopes; D005404:Fixatives; D000949:Histocompatibility Antigens Class II; D003994:Bucladesine