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

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  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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