MHC CLASS-II EXPRESSION IN DOUBLE MUTANT MICE LACKING INVARIANT CHAINAND DM FUNCTIONS

Invariant (Ii) chain and DM functions are required at distinct stages during class II maturation to promote occupancy by diverse peptide lig ands, 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 biochemic al characteristics of li(-)DM(-) doubly deficient mice, As for ii chai n mutants, their mature A alpha(b)A beta(b) dimers similarly exhibit r educed mobilities in SDS-PAGE, and in functional assays these molecule s behave as if empty or occupied by an easily displaced peptide, Addit ionally, the present experiments demonstrate that the production of fl oppy A alpha(b)A beta(b) dimers is TAP independent, In comparison with Ii chain mutants, li(-)DM(-) doubly deficient cell populations exhibi t increased peptide binding activities and consistently greater presen tation abilities in T cell stimulation assays, These functional differ ences 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 compromis ed in Ii(-)DM(-) double mutants, These mutant mice lacking both ii cha in and DM activities should prove useful for analyzing nonconventional class II Ag presentation under normal physiological conditions in the intact animal.