CD1a and MHC class I follow a similar endocytic recycling pathway.
CD1 proteins are a family of major histocompatibility complex (MHC) class I-like antigen-presenting molecules that present lipids to T cells. The cytoplasmic tails (CTs) of all human CD1 isoforms, with the exception of CD1a, contain tyrosine-based sorting motifs, responsible for the internalization of proteins by the clathrin-mediated pathway. The role of the CD1a CT, which does not possess any sorting motifs, as well as its mode of internalization are not known. We investigated the internalization and recycling pathways followed by CD1a and the role of its CT. We found that CD1a can be internalized by a clathrin- and dynamin-independent pathway and that it follows a Rab22a- and ADP ribosylation factor (ARF)6-dependent recycling pathway, similar to other cargo internalized independent of clathrin. We also found that the CD1a CT is S-acylated. However, this posttranslational modification does not determine the rate of internalization or recycling of the protein or its localization to detergent-resistant membrane microdomains (DRMs) where we found CD1a to be enriched. We also show that plasma membrane DRMs are essential for efficient CD1a-mediated antigen presentation. These findings place CD1a closer to MHC class I in its trafficking and potential antigen-loading compartments among CD1 isoforms. Furthermore, we identify CD1a as a new marker for the clathrin- and dynamin-independent and DRM-dependent pathway of internalization as well as the Rab22a- and ARF6-dependent recycling pathway.
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Duarte C
DC
Barral
Marco
M
Cavallari
Peter J
PJ
McCormick
Salil
S
Garg
Anthony I
AI
Magee
Juan S
JS
Bonifacino
Gennaro
G
De Libero
Michael B
MB
Brenner
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism / Q000502:physiology; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D046188:Protein Modification, Translational; D021122:Protein Subunits; D021381:Protein Transport; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology
D000089982:ADP-Ribosylation Factor 6; D018949:Antigens, CD1; C419393:CD1a antigen; D002966:Clathrin; D015395:Histocompatibility Antigens Class I; D021122:Protein Subunits; C484191:RAB22A protein, human; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; D020691:rab GTP-Binding Proteins