Expression and conformation of class II MHC molecules are regulated by
proinflammatory cytokines. (A) IFN-γ induces
expression of SDS-stable MHC class II on N9 cells. Cells were incubated
with or without 100 units/ml IFN-γ for 48 h before the MHC
class II proteins were immunoprecipitated (αβ-SDS stable MHC class
II complexes; α−α chain of class II, and β-β chain of class
II; nb, nonboiled; b, boiled). (B) IFN-γ up-regulates
peptide-loaded class II MHC and down-regulates empty class II surface
expression on N9 cells. Confocal microscopy (Upper) and
flow cytometry (Lower) of similarly treated cells, using
anti I-A mAb KL304 (green) and Y3P (red). (C) Microglia
cells, differentially skewed by myeloid growth factors, are able to
translocate class II MHC protein to their surfaces in response to
proinflammatory cytokines. Neonatal microglial cells incubated with
M-CSF and GM-CSF as described in Fig. 1 were washed and recultured with
10 ng/ml IFN-γ, 100 ng/ml LPS, or 100 units/ml TNFα for
48 h. Cells were collected and analyzed for surface MHC class II
expression by staining with the Y3P mAb. Normalized fluorescence
represents the ratio between the geometric mean of the Y3P staining
divided for the geometric mean of the isotype control.