The Journal of Immunology, Vol 150, Issue 2 499-507, Copyright © 1993 by American Association of Immunologists

ARTICLES

Characterization of endogenous peptides bound to purified HLA-DR molecules and their absence from invariant chain-associated alpha beta dimers

JR Newcomb and P Cresswell
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510.

We have examined peptides bound in vivo to DR alpha beta dimers and alpha beta-Invariant (I) chain complexes purified directly from a DR11, DRw52 homozygous B lymphoblastoid cell line. Nine major peptides were purified by reversed-phase HPLC from cell derived alpha beta dimers and sequenced. Eight of these were from known sources, including both endogenously synthesized and exogenous proteins. The endogenously derived peptides originated from secretory proteins, from the extracytoplasmic regions of transmembrane proteins, and from heat shock proteins. All of the peptides were from 13 to 16 amino acids in length. Comparison of the sequences of a subset of these DR-associated peptides with those of other reported DR-binding peptides suggests that an aromatic amino acid followed by a basic amino acid seven residues C- terminal from it may provide a generalizable, but not absolute, DR- binding motif, with additional residues possibly contributing to DR allelic specificity. In contrast to the alpha beta dimers, no peptides were detected bound to purified alpha beta I complexes. These data suggest that I chain-associated alpha beta dimers within the cell do not bind peptides, and provide in vivo evidence that I chain prevents the binding of inappropriate peptides to class II molecules during early stages of transport.

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