Molecular cloning of a C-type lectin superfamily protein differentially expressed by CD8 alpha(-) splenic dendritic cells

Dendritic cells (DC) are potent antigen presenting cells that activate naiv e T cells. It is becoming increasingly clear that DC are not a homogeneous cell population, but comprise different subpopulations that differ in ontog eny and function. To further the molecular characterisation of DC, we scree ned for genes that were differentially expressed amongst DC subsets and Cou ld therefore give insight into their varying biological functions. Using Re presentational Difference Analysis (RDA) we identified a gene (CIRE) that i s expressed at higher levels in the myeloid-related CD8 alpha (-) DC than i n the lymphoid-related CD8 alpha (+) DC. CIRE is a 238 amino acid type II m embrane protein, of approximately 33 kDa in size. whose extracellular regio n contains a C-type lectin domain. Northern blot analysis revealed that CIR E is almost exclusively expressed in DC and was not detected in organs Such as heart, brain, kidney, liver, and thymus. T cells failed to express mess age for CIRE, whilst B cells expressed very low levels. These data here fur ther substantiated by Northern blot analysis of 18 cell lines of various or igins (myeloid, macrophage, B and T cell) where only one cell line, which w as of myeloid origin and Could give rise to DC, expressed mRNA for CIRE. Se mi-quantitative RT-PCR suggested that CIRE is down-regulated upon activatio n. CIRE shares 57% identity with human DC-SIGN, a molecule that has been sh own to be the li,-,and of ICAM-3 and that is also a receptor that binds HIV and facilitates trans-infection of T cells. (C) 2001 Elsevier Science Ltd. All rights reserved.