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*
Department of Molecular and Cellular Biology, The Biological Laboratories, Harvard University, Cambridge, MA 02138; and
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Invariant (Ii) chain and DM functions are required at distinct
stages during class II maturation to promote occupancy by diverse
peptide ligands. The class II molecules expressed by mutant mouse
strains lacking Ii chain or DM activities display discrete structural
and functional abnormalities. The present report describes the cellular
and biochemical characteristics of
Ii-DM- doubly deficient mice. As for Ii
chain mutants, their mature A
bAßb dimers
similarly exhibit reduced mobilities in SDS-PAGE, and in functional
assays these molecules behave as if empty or occupied by an easily
displaced peptide. Additionally, the present experiments demonstrate
that the production of floppy AbAßb dimers
is TAP independent. In comparison with Ii chain mutants,
Ii-DM- doubly deficient cell populations
exhibit increased peptide binding activities and consistently greater
presentation abilities in T cell stimulation assays. These functional
differences appear to reflect higher class II surface expression
associated with their increased representation of B lymphocytes. We
also observe defective B cell maturation in mice lacking Ii chain or DM
expression, and interestingly, B cell development appears more severely
compromised in Ii-DM- double mutants. These
mutant mice lacking both Ii chain and DM activities should prove useful
for analyzing nonconventional class II Ag presentation under normal
physiological conditions in the intact animal.
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