TARGETING MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES TO THE CELL-SURFACE BY INVARIANT CHAIN ALLOWS ANTIGEN PRESENTATION UPON RECYCLING

We studied the functional consequences of targeting class II molecules to either the cell surface or to endocytic structures by expressing H LA-DR1 in human kidney cells in the presence or absence of different f orms of the invariant chain (Ii). Transfectants expressing class II mo lecules in the absence of Ii present influenza virus efficiently and c o-expression of full length Ii does not further increase antigen prese ntation. Chimeric Ii containing the cytoplasmic domain of the transfer rin receptor (Tfr-Ii) delivers class II molecules associated with Tfr- Ii to endosomal compartments, but this does not result in efficient an tigen presentation. When class II molecules are targeted to the cell s urface by Ii lacking either 15 (Delta 15Ii) or 23 (Delta 23Ii) amino a cids from the cytoplasmic domain, a fraction of free class II molecule s is also observed. Whereas Delta 15Ii did not affect antigen presenta tion by class II molecules, Delta 23Ii inhibited, but did not abrogate , the response. We show that class II molecules expressed in the prese nce of Delta 23Ii can be internalized, followed by degradation of Delt a 23Ii and return of free class II alpha beta heterodimers to the cell surface. A fraction of the resulting free class II molecules is sodiu m dodecyl sulfate stable, indicating that internalization and reappear ance of class II molecules at the cell surface can be an alternative r oute for antigen presentation. In all transfectants, class II molecule s were found in endocytic compartments that labeled for CD63 and resem bled the multilaminar MIIC compartments found in B cell lines. Ii is n ot required for endosomal targeting of class II molecules. The number of class II molecules observed in the multilaminar compartments correl ates with the efficiency of antigen presentation.