Immunohistochemical Characterization and Localization of MHC Class II Antigen-Presenting Cells in the Periodontal Ligament of Rat Incisors

The composition and location of professional antigen presenting cells (APC) varies in different mucosal surfaces. The cornea, long considered an immune-privileged tissue devoid of APCs, is now known to host a heterogeneous network of bone marrow-derived cells. Here, we utilized transgenic mice that express enhanced green fluorescent protein (EGFP) from the CD 11c promoter (pCD11c) in conjunction with immunohistochemical staining to demonstrate an interesting stratification of APCs within non-inflamed murine corneas. pCD11c+ dendritic cells (DCs) reside in the basal epithelium, seemingly embedded in the basement membrane. Most DCs express MHC class II on at least some dendrites, which extend up to 50 μm in length and traverse up 20 μm tangentially towards the apical surface of the epithelium. The DC density diminishes from peripheral to central cornea. Beneath the DCs and adjacent to the stromal side of the basement membrane reside pCD11c–CD11b+ putative macrophages that express low levels of MHC class II. Finally, MHC class II–pCD11c–CD11b+ cells form a network throughout the remainder of the stroma. This highly reproducible stratification of bone marrow-derived cells is suggestive of a progression from an APC function at the exposed corneal surface to an innate immune barrier function deeper in the stroma.

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Alternative Endogenous Protein Processing via an Autophagy-Dependent Pathway Compensates for Yersinia-Mediated Inhibition of Endosomal Major Histocompatibility Complex Class II Antigen Presentation

Infection and Immunity ◽

10.1128/iai.00155-10 ◽

2010 ◽

Vol 78 (12) ◽

pp. 5138-5150 ◽

Cited By ~ 15

Author(s):

Holger Rüssmann ◽

Klaus Panthel ◽

Brigitte Köhn ◽

Stefan Jellbauer ◽

Sebastian E. Winter ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Antigen Presentation ◽

Mhc Class Ii ◽

Virulence Factors ◽

Antigen Processing ◽

Class Ii ◽

T Cell Response ◽

Histocompatibility Complex ◽

Class Ii Antigen ◽

Mhc Class Ii Antigen

ABSTRACT Extracellular Yersinia pseudotuberculosis employs a type III secretion system (T3SS) for translocating virulence factors (Yersinia outer proteins [Yops]) directly into the cytosol of eukaryotic cells. Recently, we used YopE as a carrier molecule for T3SS-dependent secretion and translocation of listeriolysin O (LLO) from Listeria monocytogenes. We demonstrated that translocation of chimeric YopE/LLO into the cytosol of macrophages by Yersinia results in the induction of a codominant antigen-specific CD4 and CD8 T-cell response in orally immunized mice. In this study, we addressed the requirements for processing and major histocompatibility complex (MHC) class II presentation of chimeric YopE proteins translocated into the cytosol of macrophages by the Yersinia T3SS. Our data demonstrate the ability of Yersinia to counteract exogenous MHC class II antigen presentation of secreted hybrid YopE by the action of wild-type YopE and YopH. In the absence of exogenous MHC class II antigen presentation, an alternative pathway was identified for YopE fusion proteins originating in the cytosol. This endogenous antigen-processing pathway was sensitive to inhibitors of phagolysosomal acidification and macroautophagy, but it did not require the function either of the proteasome or of transporters associated with antigen processing. Thus, by an autophagy-dependent mechanism, macrophages are able to compensate for the YopE/YopH-mediated inhibition of the endosomal MHC class II antigen presentation pathway for exogenous antigens. This is the first report demonstrating that autophagy might enable the host to mount an MHC class II-restricted CD4 T-cell response against translocated bacterial virulence factors. We provide critical new insights into the interaction between the mammalian immune system and a human pathogen.

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H2-M and H2-O as Targeting Vehicles for the MHC Class II Processing Compartment Promote Antigen-Specific CD4+ T Cell Activation

Vaccines ◽

10.3390/vaccines9101053 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1053

Author(s):

Lucia Lapazio ◽

Monika Braun ◽

Kaj Grandien

Keyword(s):

T Cell ◽

Mhc Class Ii ◽

T Cell Activation ◽

Cell Activation ◽

Class Ii ◽

Cd4 T Cell ◽

Antigen Presentation Pathway ◽

Presentation Pathway ◽

Class Ii Antigen ◽

Mhc Class Ii Antigen

CD8 and CD4 T cell activation are both required for a strong and long-lasting T cell immune response. Endogenously expressed proteins are readily processed by the MHC class I antigen presentation pathway, enabling activation of CD8+ T cells. However, the MHC class II antigen presentation pathway, necessary for CD4+ T cell activation, is generally not sufficiently accessible to endogenously expressed proteins, limiting the efficiency of mRNA- or DNA-based vaccines. In the current study, we have evaluated the feasibility of using antigen sequences fused to sequences derived from the H2-M and H2-O proteins, two complexes known to participate in MHC class II antigen processing, for the enhancement of CD4 T-cell activation. We analyzed T cell activation after genetic immunization with mRNA-encoding fusion proteins with the model antigen ovalbumin and sequences derived from H2-M or H2-O. Our results show that H2-M- or H2-O-derived sequences robustly improve antigen-specific CD4 T-cell activation when fused to the antigen of interest and suggest that the approach could be used to improve the efficiency of mRNA- or DNA-based vaccines.

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