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Activation of Type B T Cells after Protein Immunization Reveals Novel Pathways of In Vivo Presentation of Peptides¹

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the National Institutes of Health. S.B.L. is a trainee of the Medical Scientist Training Program (MD/PhD).

² Address correspondence and reprint requests to Dr. Emil R. Unanue, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110. E-mail address: unanue{at}pathbox.wustl.edu

³ Abbreviations used in this paper: HEL, hen egg white lysozyme; LLO, listeriolysin O; mHEL, membrane-associated HEL; PFS, pyrogen-free saline.

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