POTENT EFFECTS OF LOW-LEVELS OF MHC CLASS II-ASSOCIATED INVARIANT CHAIN ON CD4(-CELL DEVELOPMENT() T)

Invariant chain (li)-negative mice exhibit defects in MHC class II ass embly and transport that results in reduced levels of surface class II , altered antigen presentation, and inefficient positive selection of CD4(+) T cells. Many CD4(+) T cells that do mature in ii-negative mice express a cell surface phenotype consistent with aberrant positive se lection or peripheral activation. Reconstitution of these mice with lo w levels of either the p31 or p41 form of ii does not restore transpor t of the bulk of class II or class II surface expression, but surprisi ngly does restore positive selection as measured by numbers and surfac e phenotype of CD4(+) T cells. Thus, an ii-dependent process, independ ent of effects on class II surface density, appears to be required for normal positive selection of CD4(+) T cells.