Selective release of some invariant chain-derived peptides from HLA-DR1 molecules at endosomal pH.
The predominant peptides bound to major histocompatibility complex class II molecules expressed on human B cells are derived from a relatively limited number of self proteins. To determine whether any of the prebound self peptides might be released in endosomes during recycling, water-soluble HLA-DR1 molecules were incubated with a high affinity synthetic peptide at pH 4.0 and 7.0 at 37 degrees C. The resulting bound peptide repertoire was then acid extracted, and separated by reversed-phase high performance liquid chromatography. Using a combination of mass spectrometry and ultraviolet spectroscopy, prebound self peptides and newly bound synthetic peptide were characterized. Most self peptides bound to HLA-DR1 were not appreciably released during extended exposure to pH 4.0. However, some invariant chain-derived peptides were uniquely released at this pH.
Urban
R G
RG
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Chicz
R M
RM
Strominger
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte; D001402:B-Lymphocytes / Q000378:metabolism*; D002417:Cattle; D015798:HLA-DR1 Antigen / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D015388:Organelles / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; C045084:invariant chain