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Brief Definitive Report |
ira.mellman{at}yale.edu
The association of invariant (Ii) chain with major histocompatibility complex (MHC) class II dimers is required for proper antigen presentation to T cells by antigen-presenting cells. Mice lacking Ii chain have severe abnormalities in class II transport, T cell selection, and B cell maturation. We demonstrate here that H2-M, which is required for efficient class II antigenic peptide loading, is unexpectedly downregulated in splenocytes and mature dendritic cells (DCs) from Ii–/– mice. Downregulation reflects an increased rate of degradation in Ii–/– cells. Degradation apparently occurs within lysosomes, as it is prevented by cysteine protease inhibitors such as E64, but not by the proteasome inhibitor lactacystin. Thus, Ii chain may act as a lysosomal protease inhibitor in B cells and DCs, with its deletion contributing indirectly to the loss of H2-M.
Key Words: invariant chain • H2-M • DM • cathepsin • dendritic cell
P. Pierre's present address is Centre d'Immunologie de Marseille-Luminy, Case 906, 13288 Marseille, France. E-mail: pierre@ciml.univ-mrs.fr
© 2000 The Rockefeller University Press
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