Major histocompatibility complex class I‐binding peptides are recycled to the cell surface after internalization

Ussama M. Abdel Motal, Xianzheng Zhou, Annalena Joki, Abdur Rehman Siddiqi, B. R. Srinivasa, Kristina Stenvall, Jan Dahmén, Mikael Jondal

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Cytotoxic T lymphocytes (CTL) recognize target antigens as short, processed peptides bound to major histocompatibility complex class I (MHC‐I) heavy and light chains (β2‐microglobuhn; β2 m).The heavy chain, which comprise the actual peptide binding α‐1 and α‐2 domains, can exist at the cell surface in different forms, either free, bound to β2m or as a ternary complex with β2m and peptides. MHC‐I chains are also known to internalize, and recycle to the cell surface, and this has been suggested to be important in peptide presentation. Whether MHC‐I‐bound peptides also can recycle is not known. We have investigated this by using both peptide transporter mutant RMA‐S cells and EL4 cells loaded with Db‐binding peptides, by two different approaches. First, peptides were covalently linked with galabiose (Galα4Gal) at a position which did not interfere with Db binding or immunogenicity, and peptide recycling tested with Gal2‐specific monoclonal antibodies. By flow cytometry, a return of Gal2 epitopes to the cell surface was found, after cellular internalization and cell surface clearance by pronase treatment. This peptide recycling could be discriminated from free fluid‐phase uptake and was inhibited by methylamine, chloroquine and low temperature (18°C) but not by leupeptin. Second, specific CTL were reacted with peptide‐loaded target cells after complete removal of surface Db molecules by pronase, and after different times of incubation at 37C to allow reexpression. By this procedure, reappearance of target cell susceptibility was confirmed. The results are in agreement with a model for optimizing peptide presentation by recycling through an intracellular compartment similar to early endosomes in certain antigen‐presenting cells.

Original languageEnglish
Pages (from-to)3224-3229
Number of pages6
JournalEuropean Journal of Immunology
Issue number12
Publication statusPublished - Dec 1993



  • Major histocompatibility complex class I
  • Peptide
  • RMA‐S cells
  • Recycling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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