The High-Affinity Receptor for IgE Is the Predolllinant IgE-Binding Structure in Lesional Skin of Atopic Derlllatitis Patients Radek Klubal, * Birgit Osterhoff,*·J Binghe Wang,* 2 J ean-Pi e rre Kinet,", Di e ter Maurer ,* and Georg Stingl * *Deparonent of De rmatology, Division of Immun ology, All ergy, and Infec ti ous Diseases, University of Vi enna Medi cal Schoo l, Vi enna General Ho spital and VicJ1Jla In ternational Rescarch Coo peration Center , Vienna, Austria; ·'·La bo ra tory of Allergy and Immunology, Beth Israel Hos pi tal, and Department of Patho logy, Harvard Medi ca l School, Boston, Massachusetts, U.S.A. While the skin of most patients with atopic dermati- tis (AD) is known to contain IgE-bearing cells, the contribution of the various IgE-binding structures to this phenomenon is not fully understood. To address this issue, we eluted cell-bound IgE from cryostat sections of lesional AD skin by acid treatment and performed reconstitution experiments with IgE in the absence or presence of reagents directed against the currently known IgE-binding structures. We found that incubation of acid-treated sections, with either chiIneric or serum IgE, resulted in the appearance of sizable numbers of anti-lgE-reactive cells. This cel- lular IgE loading could be entirely prevented by preincubation of the sections with the anti-FceRIa MoAb 15-1 but not with either antibodies against FceRII/CD23 and FcyRIIICD32 or with a-lactose. To exclude the possibility that acid treatment of tissue sections may have adversely influenced the IgE-bind- ing capacity of IgE receptors other than FceRI, we A !thoug h the ce ntral role of a ll ergen- sp ec ific I gE in the pathogen es is of r es pirat ory allergy is we ll estab - li shed, its co ntributi on to the eczematous le sions in c utan eo us atopy is sti ll a m atte r of co nj ecture a nd deb ate. Ev iden ce s upportin g this involvement co mes from the findings (i) that de nd,;ti c a nti ge n-presenting ce ll s (APes) in l es ion al an d, to a lesser extent , in no nl es ional skin of atopi c de mlatitis (AD) patients fi·equently ex hibit surfa ce -b ound IgE Manu sc ript received August 7, 1996; revise d Octobe r 29, 1996; accept ed for publication Nove mber 17, 1996. Reprint requests to: Dr. Radek Klubal, Vicnna International Research Coope ration Ce nt er Division of Immunology, All ergy, and Infectious Diseases, Department of Dermatology, University of Vi enna Medical School. Vi en na In ternational Research Cooperation Ce nt er, Vi cnna Inte r- national Re search Coope ra tion Center. BrUlm er Strasse 59, A-1235 Vi enna. Austria. Abbreviations: A D. ato pi c dermatitis; DC, dcndr itic ce ll; APC. antige n- presenting ce ll; KC, keratinocytc; FCERJ. hi gh-affinity [eceptor for IgE; FCERII. low-affi nity receptor for IgE/CD23 ; FcyIU[. low-affinity receptor for IgG/CD32; c1g E, mono cl onal chjme ri c IgE; s[gE, AD serum containing high titer of IgE; BlOT, bi otinylated. , Current address: Bender MedSystcms, Vi enna, Au stria. 2 Current add ress: Divi sion of Der matology. Sunnybrook Health Science Ce nter, Toronto, On tario, C anada. performed an identical series of experiments on AD skin samples that, as an exception, were essentially devoid of anti-lgE-reactive cells. Again, no IgE load- ing was detected when these sections were preincu- bated with anti-FceRIa MoAbs. In contrast, preincu- bation of the sections with a-lactose and/or MoAbs against FceRIIICD23 or FcyRIIICD32 did not affect IgE loading. Together with the observations that anti-FceRIa-reactive and IgE-binding cells are largely overlapping populations and include cells of the Langerhans ceWdendritic cell lineage, mast cells, and a few dermal dendrocytes and eosinophils, our results demonstrate that FceRI is the predominant and, perhaps, the only biologically relevant IgE- binding structure on histogenetically and function- ally diverse cell populations of AD skin. Key Ivords: Iligil-affillitJl receptor fOY IgEllgE+ alltigell-presentitlg cells. J [,west Dermatol108:336-342, 1997 mol ec ul es (Bruynze e l- Koomen e( ai, 1986; B arke r e/ ai, 1988; Bieber e/ nl, 1989a), (ii) that Langerhans ce ll (LC )-indu ce d aller ge ll- specific T ce ll activati.on and proliferation occ ur mor e e ffec tively when the aller gen is t ake n up via th ese ce lJ sUl'face -b ound IgE mo lec ul es (MlIdd e et ai , 1990), and (iii) that eczematous r eactio ns to aeroaBergens can be mo st effic ientl y indu ce d via skin regions h arbo rin g IgE-bearing de ndriti c ce lls (DCs) (Mudd e et ai, 1 990 ). By rea soning that the pr eve ntion of IgE -faciUtated a ll ergen presenta- tion co uld be an effec tiv e m eans to s top the cas cade of p at ho ge n etic eve nts occ urrin g in AD, we and others aimed to characte riz e th e IgE-bind ing s tru ctur e(s) on APCs in AD s kin. Candidate mol ec ules includ e (i) th e low- affi nity r ece p tor for IgE (F c ERlIlCD 23), a si ngl e-c hain type-II integra l me mbran e mol ec ule (Sutton and Gould , 199 3) wh ose ex pression and rel ease can be indu ce d by int e rle ukin 4/interferon-), on various ce ll types including LCs (Bieber et ai, 1989b); (ii) ga le ctin- 3, a /3- gala cto side-binding protein (B aro nd es e/ ai, 1994) pro duced by a variety of ce ll s incl udin g ke ratino cytes (KCs ) (Woll e nb e rg el ai, 1 993) , and mono cy t esl macr o phages (Lill el ai , 1995) ; a nd (iii) the high-affinity r ece p to r for IgE (FcEIU) ex presse d as a tetrameric holorecepto r on ma st cells and ba sophils (Ravet ch and Kin er, 1 991; Sutton and Gou ld, 1993). Ev iden ce for the parti ci pation of FCERIlICD23 in IgE bindin g to LCs in AD skin ca m e fi·om th e fi ndings (i) th at th e monoclonal antibody (MoAb) BBI0, supposedly directed aga inst FCERlIlCD23 0022- 202X/97/$10.50 • Co pyright © 1.997 by T he Society for In vestigative Dermatology. In c. 336