The chondroitin sulfate form of invariant chain trimerizes with conventional invariant chain and these complexes are rapidly transported from thetrans-Golgi network to the cell surface

Abstract

Targeting of MHCII-invariant chain complexes from the transGolgi network to endosomes is mediated by two di-leucinebased signals present in the cytosolic domain of invariant chain. Generation of this endosomal targeting signal is also dependent on multimerization of the invariant chain cytosolic domain sequences, mediated through assembly of invariant chain into homotrimers. A small subset of invariant chain is modified by the addition of chondroitin sulfate and is expressed on the cell surface in association with MHCII. In the present study, we have followed the biosynthetic pathway and route of intracellular transport of this proteoglycan form of invariant chain. We found that the efficiency of chondroitin sulfate modification can be increased by altering the invariant chain amino acid sequence around Ser-201 to the xylosylation consensus sequence. Our results also indicate that, following sulfation, the proteoglycan form is transported rapidly from the trans-Golgi network to the cell surface and is degraded following internalization into an endocytic compartment. Invariant chain-chondroitin sulfate is present in invariant chain trimers that also include conventional non-proteoglycan forms of invariant chain. These data indicate that invariant chain-chondroitin sulfate-containing complexes are transported rapidly from the trans-Golgi network to the cell surface in spite of the presence of an intact endosomal localization signal. Furthermore, these results suggest that invariant chainchondroitin sulfate may play an important role in the generation of cell-surface pools of invariant chain that can serve as receptors for CD44 and macrophage migration inhibitory factor.

Autoantibodies against CD74 in spondyloarthritis

“…CD74 is involved in the assembly of the major histocompatibility complex class II (MHCII) and in preventing premature binding of peptides to MHCII 15 16. In addition, CD74 has an impact on B cell differentiation 17.…”

High prevalence of anti-CD74 antibodies specific for the HLA class II-associated invariant chain peptide (CLIP) in patients with axial spondyloarthritis: Table 1

“…CD74 was shown to be involved in the assembly of major histocompatibility complex II and in preventing premature binding of peptides to it 11 12. The role of CD74 in B cell differentiation is less clear 13.…”

CD74 is a novel transcription regulator

“…At steady state, a small fraction of CD74 is expressed on the cell surface. Some of this cell-surface pool of CD74 is modified by the addition of chondroitin sulfate (2). Cell surface CD74 serves as a receptor for the cytokine, macrophage migration inhibitory factor (MIF) on many cell types (3).…”