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(Received for publication, February 19, 1997, and in revised form, April 3, 1997)
From the Department of Pathology and Program in Molecular
Cardiobiology, Human cytotoxic T lymphocytes (CTL) recognize
specific complexes of HLA class I molecules and peptides, which
assemble when nascent class I molecules bind peptides transported from
the cytoplasm into the endoplasmic reticulum by the heterodimeric
transporter associated with antigen processing (TAP). Increased class I
molecule expression on the cell surface increases the efficiency of CTL lysis. The kinetics of interferon (IFN)-
Volume 272, Number 26,
Issue of June 27, 1997
pp. 16585-16590
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Rapidly Increases Peptide Transporter (TAP)
Subunit Expression and Peptide Transport Capacity in Endothelial
Cells
,
,
Section of Immunobiology and the Howard
Hughes Medical Institute, Yale University School of Medicine,
New Haven, Connecticut 06510
induction of TAP, peptide transport capacity, and HLA class I molecule expression was determined in endothelial cells, which are targets of CTL following
transplantation or viral infection. TAP mRNAs are induced rapidly,
increasing 20-fold (TAP1) or 10-fold (TAP2) by 12 h, whereas HLA
class I mRNA is induced more slowly, increasing 10-fold in 24 h. TAP1 and TAP2 proteins are also induced rapidly, increasing 10-fold in 24 h, whereas HLA class I heavy chain proteins and surface expression increase more slowly. Peptide transport capacity in endothelial and HeLa cells increases within 6 h of IFN-
treatment, suggesting that the IFN--induced TAP heterodimers are
functional. Therefore, the IFN--induced increase in TAP proteins is
accompanied by an increased peptide transport capacity, which may be
important in supporting the subsequent rise in HLA class I protein
expression.
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