Allergy is an immune hypersensitivity reaction that affects approximately one in three Australians, often resulting in inflammatory pathology. Atopy is a specific form of allergy whereby the tendency to become sensitised to ordinary allergens results in an IgE-mediated response. Asthma, eczema and rhinitis are common consequences on atopic sensitisation. This study focused on a childhood cohort of 23 monozygotic twin pairs (n= 46, 7-12yo) which were discordant for House Dust Mite (HDM)-specific atopy. PBMCs were investigated with 12-colour flow cytometry in an allergen-naïve context. A major focus was the high-affinity IgE receptor (FcεRI [α-subunit]), which was found to be expressed by four distinct cell types following unsupervised clustering (FlowSOM, tSNE). Further investigation on the properties of these cell types found an inverse correlation between the expression intensity of FcεRIα and the Interleukin-3 receptor on conventional dendritic cells (cDC) and expression of the Interleukin-2 receptor on a subset of basophils; findings which are underreported in the literature. When compared to their non-atopic counterpart, HDM-atopic individuals displayed a reduced proportion of FcεRIα-expressing plasmacytoid DCs and cDCs. Atopic pDCs and monocytes observed reduced HLA-DR expression amongst the total cell type and those expressing FcεRIα. High affinity IgE receptor expression was substantial and universal across basophils, however the HDM-atopic twin observed significantly increased expression intensity then their non-atopic control. To gain mechanistic understanding of myeloid FcεRIα⁺ cell types, monocytes and cDCs (pooled) were isolated and analysed by RNAseq from a subset of twin pairs (n=12). 408 genes were differentially expressed between HDM-atopic and non-atopics, including genes associated with DC maturation, suppression/apoptosis and B cell regulation. Differentially expressed genes were significantly overrepresented in cytokine/receptor interaction, focal adhesion and JAK-STAT signalling pathways. These findings demonstrate unique immune cell phenotypes and indicate varied surface expression and transcriptomic profiles of monozygotic twin pairs discordant for HDM-specific atopy.