title: Adaptor protein 1 promotes cross-presentation through the same tyrosine signal in major histocompatibility complex class I as that targeted by HIV-1.
abstract: Certain antigen-presenting cells (APCs) process and present extracellular antigen with major histocompatibility complex class I (MHC-I) molecules to activate naive CD8(+) T cells in a process termed cross-presentation. We used insights gained from HIV immune evasion strategies to demonstrate that the clathrin adaptor protein adaptor protein 1 (AP-1) is necessary for cross-presentation by MHC-I molecules containing a cytoplasmic tail tyrosine signal (murine MHC-I molecules, human MHC-I HLA-A and HLA-B allotypes). In contrast, AP-1 activity was not needed for cross-presentation by MHC-I molecules containing a human MHC-I HLA-C cytoplasmic tail, which does not contain a tyrosine signal. AP-1 activity was also dispensable for presentation of endogenous antigens by MHC-I via the classical pathway. In APCs, we show that HIV Nef disrupts cross-presentation by MHC-I containing the tyrosine signal but does not affect cross-presentation by MHC-I containing the HLA-C cytoplasmic tail. Thus, we provide evidence for two separable cross-presentation pathways, only one of which is targeted by HIV.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Deanna A
authors.initials: DA
authors.lastname: Kulpa
authors.forename: Natasha
authors.initials: N
authors.lastname: Del Cid
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Peterson
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Collins
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000276:immunology / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015153:Blotting, Western; D045142:Cross-Priming / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D016086:Lentivirus; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D033961:Adaptor Protein Complex 1; D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D049452:Green Fluorescent Proteins; D014443:Tyrosine