Ai. Dodi et al., THE INVARIANT CHAIN INHIBITS PRESENTATION OF ENDOGENOUS ANTIGENS BY AHUMAN FIBROBLAST CELL-LINE, European Journal of Immunology, 24(7), 1994, pp. 1632-1639
The human fibroblast cell line, M1, expressing the products of transfe
cted DRA and DRB10101 genes (M1-DR1) was unable to present intact inf
luenza antigens to a series of DR1-restricted human T cell lines and c
lones, but was fully able to present synthetic peptides for T cell rec
ognition. In contrast, M1-DR1 cells infected with live influenza virus
were recognized by two polyclonal hemagglutinin- or whole virus-speci
fic T cell lines and one of four T cell clones. This difference could
not be accounted for simply by the ability of infectious virus to over
come a defect in antigen uptake by the M1-DR1 cells, in that direct st
udies of endocytosis showed that the M1 cells were more efficient than
human B cells in the internalization of exogenous protein. These data
suggested that the M1 cells were unable to present exogenous antigens
but were capable of loading major histocompatibility complex (MHC) cl
ass II molecules with peptides derived from endogenous antigens. To in
vestigate this further, the M1-DR1 cells were super-transfected with a
cDNA encoding the p33 and p35 forms of the human invariant chain (Ii)
. Expression of the Ii chain was detected by intracytoplasmic staining
of transfectants, and by metabolic labeling. Equimolar amounts of the
p33 and p35 forms were detected, and the high level of p35 Ii was ref
lected by extensive retention of Ii protein in the endoplasmic reticul
um. Addition of the Ii chain led to no recovery of presentation of int
act antigens with DR1, but inhibited the presentation of live virus. T
hese data indicate that MHC class II molecules in the M1-DR1 cells can
be loaded with peptides derived from endogenous proteins, possibly in
the biosynthetic pathway, and that the Ii chain has a role in limitin
g this route of class II antigen presentation.