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.
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 beta(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-beta(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.
Johnson
J M
JM
Basic Research Laboratory, National Cancer Institute, 41 Library Dr., Bethesda, MD 20892, USA.
Nicot
C
C
Fullen
J
J
Ciminale
V
V
Casareto
L
L
Mulloy
J C
JC
Jacobson
S
S
Franchini
G
G
D001692:Biological Transport; D003546:Cysteine Endopeptidases / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000378:metabolism; D015793:HLA-B7 Antigen / Q000378:metabolism; D015236:HLA-C Antigens / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000502:physiology; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; D001613:beta 2-Microglobulin / Q000378:metabolism
D015789:HLA-A2 Antigen; D015793:HLA-B7 Antigen; D015236:HLA-C Antigens; C039966:HLA-C*04 antigen; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D009856:Oncogene Proteins, Viral; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; D001613:beta 2-Microglobulin; C084305:p12I protein, Human T-lymphotropic virus 1; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex