Free Major Histocompatibility Complex Class I Heavy Chain Is Preferentially Targeted for Degradation by Human T-Cell Leukemia/Lymphotropic Virus Type 1 p12 I Protein

Author:

Johnson Julie M.1,Nicot Christophe1,Fullen Jake1,Ciminale Vincenzo2,Casareto Luca1,Mulloy James C.1,Jacobson Steve3,Franchini Genoveffa1

Affiliation:

1. Basic Research Laboratory, National Cancer Institute,1 and

2. Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy2

3. Viral Immunology Section, National Institute of Neurological Disorders and Stroke,3 Bethesda, Maryland 20892, and

Abstract

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) establishes a persistent infection in the host despite a vigorous virus-specific immune response. Here we demonstrate that an HTLV-1-encoded protein, p12 I , resides in the endoplasmic reticulum (ER) and Golgi and physically binds to the free human major histocompatibility complex class I heavy chains (MHC-I-Hc) encoded by the HLA-A2, -B7, and -Cw4 alleles. As a result of this interaction, the newly synthesized MHC-I-Hc fails to associate with β 2 -microglobulin and is retrotranslocated to the cytosol, where it is degraded by the proteasome complex. Targeting of the free MHC-I-Hc, and not the MHC-I-Hc–β 2 -microglobulin complex, by p12 I represents a novel mechanism of viral interference and disrupts the intracellular trafficking of MHC-I, which results in a significant decrease in surface levels of MHC-I on human T-cells. These findings suggest that the interaction of p12 I with MHC-1-Hc may interfere with antigen presentation in vivo and facilitate escape of HTLV-1-infected cells from immune recognition.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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