SELECTIVE RELEASE OF SOME INVARIANT CHAIN-DERIVED PEPTIDES FROM HLA-DR1 MOLECULES AT ENDOSOMAL PH

The predominant peptides bound to major histocompatibility complex cla ss II molecules expressed on human B cells are derived from a relative ly limited number of self proteins. To determine whether any of the pr ebound self peptides might be released in endosomes during recycling, water-soluble HLA-DR1 molecules were incubated with a high affinity sy nthetic 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 pepti des bound to HLA-DR1 were not appreciably released during extended exp osure to pH 4.0. However, some invariant chain-derived peptides were u niquely released at this pH.