Publication Date:
2012-11-30
Description:
Major histocompatibility complex (MHC) class II-associated antigen presentation involves an array of interacting molecules. CD74, the cell surface isoform of the MHC class II-associated invariant chain, is one such molecule; its role remains poorly defined. To address this, we have employed a high-resolution single-particle imaging method for quantifying the colocalization of CD74 with human leukocyte antigen (HLA)-DR molecules on human fibroblast cells known for their capacity to function as antigen-presenting cells. We have also examined whether the colocalization induces internalization of HLA-DR using HA 307-319 , a "universal" peptide that binds specifically to the peptide-binding groove of all HLA-DR molecules, irrespective of their alleles. We have determined that 25 ± 1.3% of CD74 and 17 ± 0.3% of HLA-DR are colocalized, and the association of CD74 with HLA-DR and the internalization of HLA-DR are both inhibited by HA 307-319 . A similar inhibition of HLA-DR internalization was observed in freshly isolated monocyte-derived dendritic cells. A key role of CD74 is to translocate HLA-DR molecules to early endosomes for reloading with peptides prior to recycling to the cell surface. We conclude that CD74 regulates the balance of peptide-occupied and peptide-free forms of MHC class II at the cell surface.—Karakikes, I., Morrison, I. E. G., O'Toole, P., Metodieva, G., Navarrete, C. V., Gomez, J., Miranda-Sayago, J. M., Cherry, R. J., Metodiev, M., Fernandez, N. Interaction of HLA-DR and CD74 at the cell surface of antigen-presenting cells by single-particle image analysis.
Print ISSN:
0892-6638
Electronic ISSN:
1530-6860
Topics:
Biology
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