Activation of type B T cells after protein immunization reveals novel pathways of in vivo presentation of peptides.
Type B T cells recognize a peptide-MHC conformer generated in recycling endosomes and eliminated by H2-DM in late endosomes; as a result, they recognize exogenous peptide, but fail to respond to the identical epitope generated from the native protein. To investigate the behavior of these cells in vivo, we generated mice transgenic for a type B TCR recognizing the 48-62 epitope of hen egg white lysozyme (HEL) presented by I-A(k). Type B T cells responded only to peptide ex vivo, but responded in vivo to immunization with either protein or peptide in the presence of Freund's adjuvant or LPS. Presentation of the type B conformer was MyD88-independent, evident within 24 h after HEL immunization, and restricted to the CD11b/c(+) APC subset. Immunization with listeriolysin O, a potent inducer of cell death, also primed type B T cells in vivo, and transfer of HEL-bearing allogeneic dendritic cells activated type B T cells. We conclude that a number of conditions in vivo, some of which induce inflammation and cell death, lead to peptide presentation through mechanisms distinct from the classical pathways involving H-2DM molecules.
Lovitch
Scott B
SB
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Esparza
Thomas J
TJ
Schweitzer
George
G
Herzog
Jeremy
J
Unanue
Emil R
ER
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology; D039481:CD11b Antigen / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D036781:Fimbriae Proteins / Q000276:immunology; D019674:Genes, T-Cell Receptor beta; D006360:Heat-Shock Proteins / Q000276:immunology; D006460:Hemolysin Proteins / Q000276:immunology; D006825:Hybridomas; D007114:Immunization; D008070:Lipopolysaccharides / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000276:immunology*; D011506:Proteins / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
D000941:Antigens; D001427:Bacterial Toxins; D039481:CD11b Antigen; D039521:CD11c Antigen; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010455:Peptides; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C022924:colonization factor antigens; D036781:Fimbriae Proteins; C517688:hen egg lysozyme (48-62); D009113:Muramidase; C038705:hlyA protein, Listeria monocytogenes