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Discordance in the Epithelial Cell-Dendritic Cell Major Histocompatibility Complex Class II Immunoproteome
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Journal Article
Discordance in the Epithelial Cell-Dendritic Cell Major Histocompatibility Complex Class II Immunoproteome
2020
Overview
Abstract
Background
Chlamydia
trachomatis and Chlamydia muridarum are intracellular bacterial pathogens of mucosal epithelial cells. CD4 T cells and major histocompatibility complex (MHC) class II molecules are essential for protective immunity against them. Antigens presented by dendritic cells (DCs) expand naive pathogen-specific T cells (inductive phase), whereas antigens presented by epithelial cells identify infected epithelial cells as targets during the effector phase. We previously showed that DCs infected by C trachomatis or C muridarum present epitopes from a limited spectrum of chlamydial proteins recognized by Chlamydia-specific CD4 T cells from immune mice.
Methods
We hypothesized that Chlamydia-infected DCs and epithelial cells present overlapping sets of Chlamydia-MHC class II epitopes to link inductive and effector phases to generate protective immunity. We tested that hypothesis by infecting an oviductal epithelial cell line with C muridarum, followed by immunoaffinity isolation and sequencing of MHC class I- and II-bound peptides.
Results
We identified 26 class I-bound and 4 class II-bound Chlamydia-derived peptides from infected epithelial cells. We were surprised to find that none of the epithelial cell class I- and class II-bound chlamydial peptides overlapped with peptides presented by DCs.
Conclusions
We suggest the discordance between the DC and epithelial cell immunoproteomes has implications for delayed clearance of Chlamydia and design of a Chlamydia vaccine.
Optimally, DCs expand antigen-specific naive T cells that recognize infected cells. We tested this postulate by determining the Chlamydia-epithelial immunoproteome. Chlamydia antigens presented to CD4 T cells by DC and epithelial cells are discordant, with major implications for vaccine development.
Publisher
Oxford University Press
Subject
/ Antigens
/ Antigens, Bacterial - immunology
/ Bacterial Vaccines - immunology
/ CD4-Positive T-Lymphocytes - immunology
/ Chlamydia Infections - immunology
/ Chlamydia Infections - microbiology
/ Chlamydia muridarum - immunology
/ Chlamydia trachomatis - immunology
/ Dendritic Cells - immunology
/ Epithelial Cells - immunology
/ Epitopes
/ Epitopes, T-Lymphocyte - immunology
/ Female
/ Histocompatibility Antigens Class I - immunology
/ Histocompatibility Antigens Class II - immunology
/ Host-Pathogen Interactions - immunology
/ Humans
/ Major histocompatibility complex
/ Mice
/ Mucosa
/ PATHOGENESIS AND HOST RESPONSE
/ Peptides
/ Vaccines
