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-Induced HLA Class II Proteins in Nonprofessional Antigen-Presenting Cells with Absence of DM and Class II Colocalization1
Departments of
*
Pediatrics,
Immunology, and
Medicine, Division of Nephrology, University of Washington, Seattle, WA 98195
We compared HLA class II expression in a human melanoma line (a
nonprofessional APC), induced by IFN-
or by stable transfection with
CIITA, with constitutive class II expression in an EBV-transformed B
lymphoblastoid cell line (a professional APC) from the same donor.
IFN--induced and CIITA-transfected melanoma cells expressed DR, DP,
and DQ at levels similar to those expressed by the professional APC;
however, DP and DQ proteins and DM-dependent DR epitopes were delayed
in appearing on the cell surface when induced by IFN-. The delay in
cell surface expression of some IFN--induced class II epitopes was
observed even though Northern blots demonstrated class II and DM genes
to be coordinately transcribed and their mRNA levels to be equivalent
to that in B lymphoblastoid cells. Confocal microscopy suggests that
discoordinate cell surface expression of class II results from
different intracellular trafficking for IFN--induced class II
proteins in the melanoma line compared with that in professional APCs.
Specifically, although DR and DM proteins were present 2 days after
IFN- induction, colocalization of DR and DM proteins intracellularly
was not apparent in cells at any time after induction. Failure of DR
and DM proteins to colocalize suggests that IFN--induced cells lack
an intracellular MIIC-like compartment. The absence of a compartment
containing DR and DM to facilitate interaction between the two proteins
may account for the delayed surface expression of class II epitopes
whose formation requires both class II and DM.
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