Binding to Ia protects an immunogenic peptide from proteolytic degradation.
A 34 amino acid hen egg-white lysozyme (HEL) peptide was designed and synthesized to investigate if an immunogenic peptide once bound to an Ia molecule becomes proteolytically inaccessible. The determinant recognized by T cells, HEL(52-61) was composed of L-amino acids whereas the 12 amino acid extension on each side of this core were composed of D-epimers. This peptide, HEL(40-73) was resistant to proteolysis, except in the core region, where any cleavage would destroy the determinant. Initially HEL(40-73) was shown to be able to stimulate the HEL specific T cell, 3A9, indicating that an I-Ak molecule can bind and present large peptides that extend beyond the theoretical binding groove. HEL(40-73) was then used to examine the proteolytic sensitivity of determinants recognized by T cells. If HEL(40-73) was treated with chymotrypsin before binding to I-Ak, the determinant was totally destroyed; however, if HEL(40-73) was allowed to first bind to I-Ak, then the determinant became resistant to chymotrypsin cleavage. Thus an Ia molecule can protect a determinant from proteolytic degradation, a finding that has important implications for proposed pathways of Ag processing.
Donermeyer
D L
DL
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Allen
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D002645:Chickens; D002918:Chymotrypsin; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006868:Hydrolysis; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D009113:Muramidase; D002918:Chymotrypsin