HLA-A2 molecules in an antigen-processing mutant cell contain signal sequence-derived peptides (original) (raw)

Nature volume 356, pages 443–446 (1992)Cite this article

Abstract

THE mutant human cell line T2 is defective in antigen presentation in the context of class I major histocompatibility complex (MHC) molecules1,2 and also in that transfected T2 cells show poor surface expression of exogenous human class I (HLA) alleles3. Both defects are thought to lie in the transport of antigenic peptides derived from cytosolic proteins into the endoplasmic reticulum (ER)1,2 as peptide-deficient class I molecules might be expected to be either unstable or retained in the ER4. The products of several mouse class I (_H_–2) genes, and the endogenous gene HLA-A2 do, however, reach the surface of T2 cells at reasonable levels although they are non-functional3,5,6. We report here that, as expected, poorly surface-expressed HLA molecules do not significantly bind endogenous peptides. Surprisingly, H–2 omolecules expressed in T2 also lack associated peptides, arguing that 'empty' complexes of mouse class I glycoproteins with human β2-microglobulin are neither retained in the ER nor unstable. HLA-A2 molecules, however, do bind high levels of a limited set of endogenous peptides. We have sequenced three of these peptides and find that two, a 9-mer and an 11-mer, are derived from a putative signal sequence (of IP-30, an interferon-γ-inducible protein7), whereas a third, a 13-mer, is of unknown origin. The unusual length of two of the peptides argues that the 9-mers normally associated with HLA-A2 molecules may be generated before their transport from the cytosol rather than in a pre-Golgi compartment. To our knowledge, this is the first report of the isolation of a fragment of a eukaryotic signal peptide generated in vivo.

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Author notes

  1. Peter Cresswell: Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, 310 Cedar Street, New Haven, Connecticut 06510, USA

Authors and Affiliations

  1. Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina, 27710, USA
    Maria L. Wei & Peter Cresswell

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  1. Maria L. Wei
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  2. Peter Cresswell
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Wei, M., Cresswell, P. HLA-A2 molecules in an antigen-processing mutant cell contain signal sequence-derived peptides.Nature 356, 443–446 (1992). https://doi.org/10.1038/356443a0

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