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*
Institut für Anthropologie und Humangenetik, Ludwig-Maximilians-Universität München, Munich, Germany;
Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensburg, Regensburg, Germany; and
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
The assembly of MHC Ia molecules in the endoplasmic reticulum
requires the presence of peptide ligands and ß2m
and is facilitated by chaperones in an ordered sequence of molecular
interactions. A crucial step in this process is the interaction of the
class I 
-chain/ß2m dimer with TAP, which is believed
to ensure effective peptide loading of the empty class I molecule. We
have previously demonstrated impaired intracellular transport of the
class Ib molecule HLA-E in mouse myeloma cells cotransfected with the
genes for HLA-E and human ß2m, which is most likely
attributable to inefficient intracellular peptide loading of the HLA-E
molecule. We therefore analyzed the ability of HLA-E in the
transfectant cell line to bind synthetic peptides by means of their
ability to enhance cell surface expression of HLA-E. Peptide binding
was confirmed by testing the effect on the thermostability of soluble
empty HLA-E/human ß2m dimers. Two viral peptides binding
to HLA-E were thus identified, for which the exact positioning of the N
terminus appeared critical for binding, whereas the contribution of the
length of the C terminus seemed to be minor, allowing peptides as short
as seven amino acids and up to 16 amino acids to exhibit considerable
binding activity. Furthermore, we demonstrate that HLA-E interacts with
TAP and that this interaction can be prolonged by the proteasome
inhibitor
N-acetyl-L-leucyl-L-leucyl-L-norleucinal,
which reduces the intracellular peptide pool. The presented data
indicate that HLA-E is capable of presenting peptide ligands similar to
the repertoire of HLA class Ia molecules.
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