Antigen presentation by Langerhans cells

doi:10.1016/j.coi.2012.11.007

Current Opinion in Immunology

Volume 25, Issue 1, February 2013, Pages 115-119

https://doi.org/10.1016/j.coi.2012.11.007 Get rights and content

Langerhans cells and other skin-resident dendritic cells (DC) are required for the development of cutaneous adaptive immune responses. In vivo experiments using mice with selective DC-subset deficiencies and ex vivo experiments using isolated DC suggests that each subset makes a unique contribution to the adaptive response. This review focuses on the functional outcome of antigen presentation by Langerhans cells. Special attention is given to their ability to promote CD4 T cell differentiation in a variety of inflammatory contexts and whether this subset has the capacity to cross-prime CD8 T cells.

Highlights

► CD103+ dDC, not LC are responsible for cross-priming. ► LC promote Th17 in response to extracellular pathogens. ► LC promote Th2 in response to epicutaneous immunization. ► Presentation by LC may result in T cell anergy/deletion.

Introduction

Langerhans cells (LC) are the sole dendritic cell (DC) in the epidermis, the outermost layer of the skin. They have been a focus of intense study since their identification as an antigen-presenting cell in the mid 1970s and were considered as the proto-typical tissue DC on which the ‘DC paradigm’ was based [1, 2, 3]. Their location at a barrier surface provides them with early access to skin pathogens, commensal organisms, foreign chemicals (a.k.a. contact sensitizers) as well as to epidermal self-antigens. A considerable body of work suggests that LC transport these antigens to regional lymph nodes where they present to naïve T cells thereby initiating adaptive cutaneous immune responses. Despite this, their function remains stubbornly enigmatic. Functional studies in mice suggest that many of the properties initially ascribed to LC are performed by CD103+ dermal DC and that LC have the capacity to both initiate and suppress cutaneous immune responses. This debate has been extensively examined elsewhere [4, 5] and will not be covered in this review. Rather, we will focus on the question of how does the interaction between LC and T cells affect the development of antigen-specific responses.

Section snippets

LC and cross presentation

Cross presentation is the capacity of an antigen-presenting cell to acquire exogenous antigen and present the processed peptides in the context of MHC-I. This function is critically important for the development of self-tolerance as well as for CTL responses against most tumors and viruses that do not infect antigen-presenting cells. Not all DC have the capacity for cross presentation and targeting antigen to those DC subsets that can induce a CTL response has been a focus of vaccine

Antigen presentation to CD4 cells

The capacity of LC to promote CD4 T cell proliferation has been well established [29, 30, 31, 32, 33]. It is less clear, though, how antigen-presentation by LC affects the development of Th phenotypes, tolerance, and/or the establishment of memory. There is a rich literature exploring the role of LC in a wide variety of biological processes (e.g. CHS and skin infection) that has been recently reviewed [4, 5]. We will focus on those experiments in which responses to specific peptide antigens

Summary

There has been considerable progress understanding the function of LC in the past few years. As is often the case, there are conflicting data and multiple experimental approaches that must be reconciled. It is now clear that in the skin-draining LN, CD103+ dDC are responsible for cross-priming naïve T cells and LC promote Th17 responses to extracellular pathogens, though exclusive stimulation of CD4 T cells by LC may ultimately lead to tolerance/anergy. The possibility that LC activate

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

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^☆: This work was supported by a grant from the NIH AR056632 and AR060794 and the American Skin Association. BZI was supported by a grant from the Dermatology Foundation.

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Antigen presentation by Langerhans cells☆

Highlights

Introduction

Section snippets

LC and cross presentation

Antigen presentation to CD4 cells

Summary

References and recommended reading

J Invest Dermatol

Trends Immunol

Immunity

Nat Immunol

Immunity

J Exp Med

J Exp Med

J Allergy Clin Immunol

Dendritic cells and the control of immunity

Nature

Origin, homeostasis and function of Langerhans cells and other Langerin-expressing dendritic cells

Nat Rev Immunol

Langerhans cells and more: Langerin-expressing dendritic cell subsets in the skin

Immunol Rev

Immunobiology of dendritic cells

Annu Rev Immunol

Cross-presentation by dendritic cells

Nat Rev Immunol

Langerhans cells cross-present antigen derived from skin

Proc Natl Acad Sci USA

Skin inflammation is not sufficient to break tolerance induced against a novel antigen

J Immunol

Langerhans cells are not required for the CD8 T cell response to epidermal self-antigens

J Immunol

Deletional self-tolerance to a melanocyte/melanoma antigen derived from tyrosinase is mediated by a radio-resistant cell in peripheral and mesenteric lymph nodes

J Immunol

Cutting edge: langerin/CD207 receptor on dendritic cells mediates efficient antigen presentation on MHC I and II products in vivo

J Immunol