Adaptor Protein 1 Promotes Cross-Presentation through the Same Tyrosine Signal in Major Histocompatibility Complex Class I as That Targeted by HIV-1 |
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Authors: | Deanna A Kulpa Natasha Del Cid Kirsten A Peterson Kathleen L Collins |
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Institution: | Department of Internal Medicinea;Department of Microbiology and Immunology,b University of Michigan, Ann Arbor, Michigan, USA |
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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. |
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