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MHC class l/β2-microglobulin complexes associate with TAP transporters before peptide binding

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Abstract

MAJOR histocompatibility complex class I molecules bind antigenic peptides in the endoplasmic reticulum (ER) and transport them to the cell surface for recognition by cytotoxic T lymphocytes. The peptides are predominantly generated from cytoplasmic proteins, probably by the action of the multicatalytic proteinase complex, or proteasome1,2. They are transported into the ER by the transporters associated with antigen processing (TAP), a complex formed from two subunits, TAP.l and TAP.2 (refs 3–5). Here we show that the TAP molecules are intimately involved in the assembly of the class I/β2-microglobulin (β2m) peptide complex. Free class I heavy chains are associated in the ER with the chaperone calnexin6,7. In human B-cell lines, however, class I/β2m dimers in the ER are physically associated with TAP molecules rather than calnexin. Our results suggest that calnexin mediates class I/β2m dimerization, and subsequent binding of the dimers to TAP molecules facilitates their association with TAP-transported peptides.

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Authors and Affiliations

  1. Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, 310 Cedar Street, New Haven, Connecticut, 06520, USA

    Bodo Ortmann, Matthew J. Androlewicz & Peter Cresswell

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  1. Bodo Ortmann
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  2. Matthew J. Androlewicz
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  3. Peter Cresswell
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Ortmann, B., Androlewicz, M. & Cresswell, P. MHC class l/β2-microglobulin complexes associate with TAP transporters before peptide binding. Nature 368, 864–867 (1994). https://doi.org/10.1038/368864a0

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  • DOI: https://doi.org/10.1038/368864a0

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