This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lo, W.-F. Articles by Soloski, M. J. Search for Related Content PubMed PubMed Citation Articles by Lo, W.-F. Articles by Soloski, M. J.

 Previous Article  |  Next Article 

Infection and Immunity, May 2004, p. 2843-2849, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2843-2849.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Bacterial and Host Factors Involved in the Major Histocompatibility Complex Class Ib-Restricted Presentation of Salmonella Hsp 60: Novel Pathway

Wei-Feng Lo,^1, Cory D. Dunn,² Helena Ong,¹ Eleanor S. Metcalf,³ and Mark J. Soloski^1*

Division of Molecular and Clinical Rheumatology, Department of Medicine,¹ Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205,² Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814³

Received 22 July 2003/ Returned for modification 28 October 2003/ Accepted 13 February 2004

Previously, a peptide epitope derived from the Hsp 60 molecule of Salmonella that is presented by the major histocompatibility complex (MHC) class Ib molecule Qa-1 to CD8⁺ cytotoxic T cells (CTLs) was described. In the present study we investigated the Salmonella-induced processing and presentation pathway for generating this Qa-1-restricted epitope. Live bacteria and, to a lesser extent, opsonized heat-killed bacteria are able to sensitize target cells for lysis by Salmonella-specific CTL. In contrast, heat-killed bacteria cannot sensitize target cells. Presentation of the Hsp 60 epitope appears independent of bacterial internalization, because cytochalasin D does not affect presentation. Moreover, Salmonella strains defective in the InvA or InvE operon, two critical components of the type III secretion pathway, are as efficient as wild-type Salmonella enterica serovar Typhimurium in sensitizing infected targets to lysis. Collectively, these results suggest the existence of a novel antigen-processing pathway in which exogenous antigens gain access to the cytosolic MHC class I processing machinery. Considering the abundant nature of bacterial Hsp 60 and the upregulation of this protein after Salmonella infection of eukaryotic cells, this mode of antigen presentation may be particularly relevant to understanding the host defense mechanisms against gram-negative bacteria.

Editor: F. C. Fang

Present address: Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.