Major histocompatibility complex class II-peptide complexes internalize using a clathrin- and dynamin-independent endocytosis pathway.
Major histocompatibility complex (MHC) class II molecules (MHC-II) function by binding antigenic peptides and displaying these peptides on the surface of antigen presenting cells (APCs) for recognition by peptide-MHC-II (pMHC-II)-specific CD4 T cells. It is known that cell surface MHC-II can internalize, exchange antigenic peptides in endosomes, and rapidly recycle back to the plasma membrane; however, the molecular machinery and trafficking pathways utilized by internalizing/recycling MHC-II have not been identified. We now demonstrate that unlike newly synthesized invariant chain-associated MHC-II, mature cell surface pMHC-II complexes internalize following clathrin-, AP-2-, and dynamin-independent endocytosis pathways. Immunofluorescence microscopy of MHC-II expressing HeLa-CIITA cells, human B cells, and human DCs revealed that pMHC enters Arf6(+)Rab35(+)EHD1(+) tubular endosomes following endocytosis. These data contrast the internalization pathways followed by newly synthesized and peptide-loaded MHC-II molecules and demonstrates that cell surface pMHC-II internalize and rapidly recycle from early endocytic compartments in tubular endosomes.
Walseng
Even
E
Experimental Immunology Branch, NCI, NIH, Bethesda, MD 20892, USA.
Bakke
Oddmund
O
Roche
Paul A
PA
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D033962:Adaptor Protein Complex 2 / Q000235:genetics / Q000378:metabolism; D017951:Antigen Presentation / Q000276:immunology; D002966:Clathrin / Q000235:genetics / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010455:Peptides / Q000737:chemistry*; D020691:rab GTP-Binding Proteins / Q000378:metabolism
D000089982:ADP-Ribosylation Factor 6; D033962:Adaptor Protein Complex 2; D002966:Clathrin; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C511183:RAB35 protein, human; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; D020691:rab GTP-Binding Proteins; D034281:Dynamins