Antigen presentation: lysoyme, autoimmune diabetes, and Listeria--what do they have in common?
We discuss three areas of antigen presentation and macrophage biology being investigated in the laboratory. Using hen egg-white lysozyme as a protein antigen, all the segments of the molecules selected by the class II histocompatibility molecule I-A(k) were identified and characterized. The display of each family of peptides was explained biochemically and quantitated. Conformational isomers of a peptide-major histocompatibility complex (MHC) complex were identified. The relationship between the amounts of peptide-MHC displayed by the antigen-presenting cells and two biologic responses, central thymic selection and T-cell responses after immunization in adjuvant, were examined. The class II MHC molecule of the nonobese diabetic I-Ag7 is being examined for its properties of peptide selection. The objective is to identify the diabetogenic peptides, as well as the repertoire of protein antigens from beta-cells that trigger autoantibodies. The I-Ag7 molecule selects peptides that show very distinctive sequence motifs: one or more acidic residues at the carboxy terminus that interact at the P9 pocket of the binding groove. Finally, the investigations in listeriosis examined the early events in immune induction. More important, we found that Listeria causes marked apoptosis of lymphocytes around infective foci resulting from the apoptogenic properties of the pore-forming molecule Listeriolysin O.
Unanue
Emil
E
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. unanue@pathbox.wustl.edu
Byersdorfer
Craig
C
Carrero
Javier
J
Levisetti
Matteo
M
Lovitch
Scott
S
Pu
Zheng
Z
Suri
Anish
A
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000737:chemistry / Q000235:genetics; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies; D002645:Chickens; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D008088:Listeriosis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D018448:Models, Immunological; D009113:Muramidase / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000941:Antigens; D001323:Autoantibodies; D000939:Epitopes; D009113:Muramidase