Pretreatment of Stimulator/Target Cells with Xyloside Inhibits Synthesis of the Class II Associated Proteoglycan, but Potentiates an MLR and Antigen Presentation

Identification of the glycosaminoglycan-attachment site of mouse invariant-chain proteoglycan core protein by site-directed mutagenesis.

“…The concept that GAG is useful in antigen-presenting-cell function is consistent with the observation that xylosides, which inhibit proteoglycan synthesis (58), diminish the capacity of spleen cells to serve as antigen-presenting cells (16,17). However, although the xyloside inhibition data show that proteoglycans play an important role in antigen processing and/or presentation, it is not clear that this finding is due to a specific effect on Ii-CS.…”

“…This complex of surface-expressed processed antigen and Ia is bound by the T-cell antigen receptor, leading to helper-T-lymphocyte activation and release of soluble lymphokines from the T cell. The observations that Ii-CS is associated with Ia during terminal biosynthesis (9)(10)(11) and at the cell surface (11) and that interference with the synthesis of Ii-CS is accompanied by loss of antigen-presenting function (16,17) suggest some possible roles for Ii-CS in Ia biology. The Ii-CS molecule may enhance the binding between antigen-presenting cell and T cell, or it may affect Ia trafficking in ways that influence the association of Ia with processed antigen.…”

“…Thus, the function of Ii has not been determined. Treatment of antigen-presenting cells with inhibitors of GAG addition (xylosides) interferes with their ability to present antigen to T cells, suggesting that li-CS may have a specialized role in helper-T-cell recognition (16,17). In order to examine the role of Ii-CS more specifically, and to understand the biochemistry of Ii biosynthesis and GAG addition, we made a site-specific mutation in the predicted site of GAG addition in Ii.…”