Cell
Volume 71, Issue 6, 11 December 1992, Pages 963-972
Journal home page for Cell

Article
Expression of a membrane protease enhances presentation of endogenous antigens to MHC class I-restricted T lymphocytes

https://doi.org/10.1016/0092-8674(92)90392-PGet rights and content

Abstract

We find that expression of the membrane dipeptidyl carboxypeptidase angiotensin-converting enzyme (ACE) enhances presentation of certain endogenously synthesized peptides to major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes. ACE appears to function only in an intracellular secretory compartment of antigen-presenting cells. ACE-enhanced antigen presentation requires the expression of the putative antigenic peptide transporters, TAP1 and TAP2. These findings demonstrate that a protease can influence the processing of endogenously synthesized antigens and strongly suggest that longer peptides can be transported from the cytosol to a secretory compartment where trimming of antigenic peptides to the lengths preferred by MHC class I molecules can occur if the appropriate protease is present.

References (47)

  • J.R. Bennink et al.

    Recognition of cloned influenza virus hemagglutinin gene products by cytotoxic T lymphocytes

    J. Virol.

    (1986)
  • P.J. Bjorkman et al.

    The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens

    Nature

    (1987)
  • V. Cerundolo et al.

    Presentation of viral antigen controlled by a gene in the major histocompatibility complex

    Nature

    (1990)
  • V. Cerundolo et al.

    The binding affinity and dissociation rates of peptides for class I major histocompatibility complex molecules

    Eur. J. Immunol.

    (1991)
  • S. Chakrabarti et al.

    Vaccinia virus expression vector: coexpression of β-galactosidase provides visual screening of recombinant virus plaques

    Mol. Cell. Biol.

    (1985)
  • J.H. Cox et al.

    Antigen presentation requires transport of MHC class I molecules from the endoplasmic reticulum

    Science

    (1990)
  • J.H. Cox et al.

    Retention of adenovirus E19 glycoprotein in the endoplasmic reticulum is essential to its ability to block antigen presentation

    J. Exp. Med.

    (1991)
  • E. Deverson et al.

    MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters

    Nature

    (1990)
  • M.R.W. Ehlers et al.

    Angiotensin-converting enzyme: new concepts concerning its biological role

    Biochemistry

    (1989)
  • L.C. Eisenlohr et al.

    Flanking sequences influence the presentation of an endogenously synthesized peptide to cytotoxic T lymphocytes

    J. Exp. Med.

    (1992)
  • T. Elliot et al.

    Peptide-induced conformational change of the class I heavy chain

    Nature

    (1991)
  • K. Falk et al.

    Cellular peptide composition governed by major histocompatibility complex class I molecules

    Nature

    (1990)
  • K. Falk et al.

    Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules

    Nature

    (1991)
  • Cited by (0)

    Present address: Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.

    View full text