Free major histocompatibility complex class I heavy chain is preferentially targeted for degradation by human T-cell leukemia/lymphotropic virus type 1 p12I protein

J. M. Johnson, C. Nicot, J. Fullen, V. Ciminale, L. Casareto, J. C. Mulloy, S. Jacobson, G. Franchini

Research output: Contribution to journalArticlepeer-review

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, p12I, 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 β2-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-β2-microglobulin complex, by p12I 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 p12I with MHC-I-Hc may interfere with antigen presentation in vivo and facilitate escape of HTLV-I-infected cells from immune recognition.

Original languageEnglish
Pages (from-to)6086-6094
Number of pages9
JournalJournal of Virology
Volume75
Issue number13
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Immunology

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