The Dendritic Cell Subtype-restricted C-type Lectin Clec9A is a Target for Vaccine Enhancement

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2008 Aug 2

PMID 18669894

Citations 218

Authors

Irina Caminschi

Anna I Proietto

Fatma Ahmet

Susie Kitsoulis

Joo Shin Teh

Jennifer C Y Lo

Alexandra Rizzitelli

Li Wu

David Vremec

Serani L H van Dommelen

Ian K Campbell

Eugene Maraskovsky

Hal Braley

Gayle M Davey

Patricia Mottram

Nicholas Van de Velde

Kent Jensen

Andrew M Lew

Mark D Wright

William R Heath

Ken Shortman

Mireille H Lahoud

Affiliations

Soon will be listed here.

Abstract

A novel dendritic cell (DC)-restricted molecule, Clec9A, was identified by gene expression profiling of mouse DC subtypes. Based on sequence similarity, a human ortholog was identified. Clec9A encodes a type II membrane protein with a single extracellular C-type lectin domain. Both the mouse Clec9A and human CLEC9A were cloned and expressed, and monoclonal antibodies (mAbs) against each were generated. Surface staining revealed that Clec9A was selective for mouse DCs and was restricted to the CD8(+) conventional DC and plasmacytoid DC subtypes. A subset of human blood DCs also expressed CLEC9A. A single injection of mice with a mAb against Clec9A, which targets antigens (Ags) to the DCs, produced a striking enhancement of antibody responses in the absence of added adjuvants or danger signals, even in mice lacking Toll-like receptor signaling pathways. Such targeting also enhanced CD4 and CD8 T-cell responses. Thus, Clec9A serves as a new marker to distinguish subtypes of both mouse and human DCs. Furthermore, targeting Ags to DCs with antibodies to Clec9A is a promising strategy to enhance the efficiency of vaccines, even in the absence of adjuvants.

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