PRESENTATION OF A CYTOSOLIC ANTIGEN BY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES REQUIRES A LONG-LIVED FORM OF THE ANTIGEN

Class I and class II molecules of the major histocompatibility complex present peptides to T cells, Class I molecules bind peptides that har e been generated in the cytosol by proteasomes and delivered into the endoplasmic reticulum by the transporter associated with antigen prese ntation, In contrast, class II molecules are very efficient in the pre sentation of antigens that have been internalized and processed in end osomal lysosomal compartments, In addition, class II molecules can pre sent some cytosolic antigens by a TAP-independent pathway. To test whe ther this endogenous class II presentation pathway was linked to prote asome-mediated degradation of antigen in the cytosol, the N-end rule w as utilized to produce two forms of the influenza virus matrix protein with different in vivo half-lives (10 min vs. 5 h) when expressed in human B cells, Whereas class I molecules presented both the short- and the long-lived matrix proteins, class II molecules presented exclusiv ely the long-lived form of antigen, Thus, rapid degradation of matrix protein in the cytosol precluded its presentation by class II molecule s, These data suggest that the turnover of long-lived cytosolic protei ns, some of which is mediated by delivery into endosomal/lysosomal com partments, provides a mechanism for immune surveillance by CD4(+) T ce lls.