Amino-Terminal Trimming of Peptides for Presentation on Major Histocompatibility Complex Class II Molecules

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 2; pp. 628 - 633
• Main Authors: Nelson, Christopher A., Vidavsky, Ilan, Viner, Nicholas J., Gross, Michael L., Unanue, Emil R.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 21.01.1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antigen presenting cells; Antigen-Presenting Cells - immunology; Antigens; Antigens - metabolism; Biological Sciences; Endopeptidases - metabolism; Enzymes; Histocompatibility Antigens Class II - immunology; Hybridomas; Immunity (Disease); Major histocompatibility complex genes; Mass spectra; Mass Spectrometry; Mass spectroscopy; Mice; Molecular Sequence Data; Molecules; Muramidase - chemistry; Muramidase - immunology; Peptides; Peptides - immunology; Peptides - metabolism; Structure-Activity Relationship; T lymphocytes; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.2.628

Major histocompatibility complex (MHC) class II molecules bind antigenic peptides for display to T lymphocytes. Although the enzymes involved remain to be identified, it is commonly believed that class II associated peptides are released from intact antigens through a series of proteolytic steps carried out inside antigen presenting cells. We have examined the effect of amino acid substitutions on proteolytic processing of the model antigen hen-egg lysozyme (HEL). Altered HEL molecules, engineered by site-directed mutagenesis of a HEL cDNA, were expressed as separate stable transfectants in a B cell lymphoma line. Each transfectant processed a different mutant HEL protein for presentation on MHC class II. We purified the resulting class II-associated peptides and analyzed them by mass spectrometry. Our results strongly support the hypothesis that antigen processing continues after peptide binding to the MHC class II molecule and are most consistent with a scenario in which long peptides first bind to MHC class II and are then trimmed by exopeptidase.