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CD8⁺ T Cell Protective Immunity against Chlamydia pneumoniae Includes an H2-M3-Restricted Response That Is Largely CD4⁺ T Cell-Independent¹

Department of Microbiology and Immunology, University of Texas Health Center, Tyler, TX 75708

CD8⁺ T cells are important for immunity to the intracellular bacterial pathogen Chlamydia pneumoniae (Cpn). Recently, we reported that type 1 CD8⁺ (Tc1) from Cpn-infected B6 mice recognize peptides from multiple Cpn Ags in a classical MHC class Ia-restricted fashion. In this study, we show that Cpn infection also induces nonclassical MHC class Ib-(H2-M3)-restricted CD8⁺ T cell responses. H2-M3-binding peptides representing the N-terminal formylated sequences from five Cpn Ags sensitized target cells for lysis by cytolytic effectors from the spleens of infected B6 mice. Of these, only peptides fMFFAPL (P1) and fMLYWFL (P4) stimulated IFN- production by infection-primed splenic and pulmonary CD8⁺ T cells. Studies with Cpn-infected K^b–/–/D^b–/– mice confirmed the Tc1 cytokine profile of P1- and P4-specific CD8⁺ T cells and revealed the capacity of these effectors to exert in vitro H2-M3-restricted lysis of Cpn-infected macrophages and in vivo pulmonary killing of P1- and P4-coated splenocytes. Furthermore, adoptive transfer of P1- and P4-specific CD8⁺ T cells into naive K^b–/–/D^b–/– mice reduced lung Cpn loads following challenge. Finally, we show that in the absence of MHC class Ia-restricted CD8⁺ T cell responses, CD4⁺ T cells are largely expendable for the control of Cpn growth, and for the generation, memory maintenance, and secondary expansion of P1- and P4-specific CD8⁺ T cells. These results suggest that H2-M3-restricted CD8⁺ T cells contribute to protective immunity against Cpn, and that chlamydial Ags presented by MHC class Ib molecules may represent novel targets for inclusion in anti-Cpn vaccines.

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 Grant RO1 HL70641 from the National Institutes of Health.

² Address correspondence and reprint requests to Dr. Benjamin Wizel, Department of Microbiology and Immunology, University of Texas Health Center, 11937 U.S. Highway 271, Tyler, TX 75708. E-mail address: bwizel{at}uthct.edu

³ Abbreviations used in this paper: Cpn, Chlamydia pneumoniae; N-fM, N-terminal formylated methionine; Tc1, type 1 CD8⁺ T cell; IFU, inclusion-forming unit; TCM, T cell medium; i.n., intranasal; MFI, mean fluorescence intensity; LMNC, lung mononuclear cell; SC, spleen cell; mAM, murine alveolar macrophage; SFC, spot-forming cell; SmpB, small protein B.