Antigen presentation by Langerhans cells☆
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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