Cross-presentation of Disialoganglioside GD3 to Natural Killer T Cells

Author:

Wu Dianna Y.12,Segal Neil H.12,Sidobre Stephane3,Kronenberg Mitchell3,Chapman Paul B.12

Affiliation:

1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021

2. Swim Across America Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY 10021

3. La Jolla Institute for Allergy and Immunology, San Diego, CA 92121

Abstract

GD3, a ganglioside expressed on human melanoma, can be recognized by the humoral immune system. In this paper, we demonstrate that immunizing mice with the human melanoma cell line SK-MEL-28 (GD3+ GM2− CD1−) or with syngeneic APCs loaded with GD3 can induce a GD3-reactive natural killer T (NKT) cell response. GD3-reactive NKT cells were detected among splenocytes of immunized mice at frequencies of ∼1:2,000 both by ELISPOT and GD3-loaded mouse CD1d tetramer analysis. GD3-reactive NKT cells did not react with GM2, a closely related ganglioside, and were not detectable in unimmunized mice. GD3-reactive NKT cells initially produced IL-4 and IFN-γ followed by IL-10. They were CD1d restricted in that reactivity was abrogated when APCs were blocked with anti-CD1d monoclonal antibody before being loaded with GD3 or when APCs from CD1d knockout mice were used. Because SK-MEL-28 does not express any isoform of human CD1, GD3 must be cross-presented by murine APCs in vivo. This is the first analysis of a natural ligand for mouse NKT cells and the first definitive paper of cross-presentation to NKT cells. This could be a mechanism for NKT cell recognition of tumor gangliosides in CD1− tumors.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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