Inhibition of proteoglycan synthesis eliminates the proteoglycan form of Ia-associated invariant chain and depresses antigen presentation

A possible role for invariant chain (Ii)² as a regulator of Ia expression at the cell surface has been proposed, and suggestive evidence that Ii facilitates Ia expression at the cell surface has been presented. We now know about an alternative proteoglycan form of the Ii that bears a chondroitin sulfate (CS) glycosaminoglycan (GAG). This Ii proteoglycan (Ii-CS) is associated with Ia α-β dimers at the cell surface, and it is possible that this Ii-CS form of Ii is involved in the facilitation of α-β expression or in Ia recognition. One way to examine these possibilities is to selectively interfere with the conversion of Ii to Ii-CS by using a competitive substrate for GAG synthesis, p-nitrophenyl β-D-xyloside (PNP-xyloside). After treating cells with PNP-xyloside, we found that Ii-CS synthesis was depressed, whereas the synthesis of Ia α,β and conventional Ii appeared to be unaffected. Under these circumstances, Ia was still detectable at the cell surface, but the PNP-xyloside-treated cells were less effective in presenting antigen to responsive T cells.