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Review
. 2022 May 9:13:860915.
doi: 10.3389/fimmu.2022.860915. eCollection 2022.

Antigen Presentation in the Lung

Takumi Kawasaki  1 , Moe Ikegawa  1 , Taro Kawai  1
Affiliations
Review

Antigen Presentation in the Lung

Takumi Kawasaki et al. Front Immunol. .

Abstract

The lungs are constantly exposed to environmental and infectious agents such as dust, viruses, fungi, and bacteria that invade the lungs upon breathing. The lungs are equipped with an immune defense mechanism that involves a wide variety of immunological cells to eliminate these agents. Various types of dendritic cells (DCs) and macrophages (MACs) function as professional antigen-presenting cells (APCs) that engulf pathogens through endocytosis or phagocytosis and degrade proteins derived from them into peptide fragments. During this process, DCs and MACs present the peptides on their major histocompatibility complex class I (MHC-I) or MHC-II protein complex to naïve CD8+ or CD4+ T cells, respectively. In addition to these cells, recent evidence supports that antigen-specific effector and memory T cells are activated by other lung cells such as endothelial cells, epithelial cells, and monocytes through antigen presentation. In this review, we summarize the molecular mechanisms of antigen presentation by APCs in the lungs and their contribution to immune response.

Keywords: antigen cross presentation; antigen presentation; dendritic cells; lung; macrophages.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Antigen presentation on MHC-II molecule. Extracellular antigens are endocytosed or phagocytosed, and intracellular antigens are translocated to the late-endosome or the lysosome via autophagosome- or LAMP-2A- mediated autophagy. Then these antigens are degraded by asparaginyl endopeptidase and cathepsin. MHC-II is synthesized in ER and mainly pooled at the plasma membrane as MHC-II-Ii chain complex. When the complex translocates from the ER or the plasma membrane to the acidic compartment, Ii chain is degraded into CLIP and driven out by interaction with H2-M. Afterward, antigen peptides bind to the MHC-II and the peptide-MHC-II complex exports to the cell surface.
Figure 2
Figure 2
Antigen cross-presentation on MHC-I molecule. Extracellular antigens are presented via “vacuolar pathway” or “cytosolic pathway” in the cross-presentation pathway. In the vacuolar pathway, endocytosed antigen peptides are degraded by cathepsin S and bind to MHC-I in the endosomal compartment. In the cytosolic pathway, endocytosed or phagocytosed extracellular antigens are translocated to the cytosol via Sec61 and degraded by proteasome. The degraded peptides are transported into the ER or the endosome via TAP and trimmed by ERAP (in the ER) or IRAP (in the endosomes). TAP form PLC with MHC-I, ERp57 and calreticulin. Afterward, the trimmed peptides bind to the MHC-I and transported to the cell surface. The MHC-I in the endosomes is recruited from the plasma membrane through Rab11a+ recycle endosome, the ER, or the ERGIC. Antigen degradation regulated by the acidification in the endosome, the phagosome, and the lysosome by V-ATPase. On the other hand, NADPH oxidase NOX2 regulates phagosomal alkalization and is recruited to the phagosomes by Rab27a-dependent pathway.
Figure 3
Figure 3
Antigen presenting cells in the lung. The lungs are constantly exposed to environmental and infectious agents such as dust, viruses, fungi, and bacteria that invade the lungs upon breathing. The lungs are protected by various types of immune cells and epithelial cells. Lung DCs are largely divided into three major subsets and are broadly subdivided into pDCs, cDC1s and cDC2s. MACs in the lungs consist of two major populations: AMs and IMs. LECs consist of ATI and ATII cells in the alveoli, and the endothelial cells and other types of cells constituting the bronchial airway epithelium. Monocytes migrate to the lungs in response to inflammatory stimuli in a CCR2-dependent manner and these cells differentiate to moDCs or AMs. Small blood vessels allow oxygen to be extracted from the air into the blood, and carbon dioxide to be released from the blood into the air. The cells lining the inner surface of blood vessels are the pulmonary endothelial cells. These cells function as APCs that engulf pathogens through endocytosis or phagocytosis and present their peptides on major MHC-I or MHC-II protein complex to CD8+ or CD4+ T cells.
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