Summary
GD3, a ganglioside expressed on melanoma, is the only tumour‐associated glycolipid described to date that can induce a CD1d‐restricted natural killer T (NKT)‐cell response. We analysed the fine specificity of GD3‐reactive NKT cells and discovered that immunization with GD3 induced two populations of GD3‐reactive NKT cells. One population was CD4+ CD8− and was specific for GD3; the other population was CD4− CD8− and cross‐reacted with GM3 in a CD1d‐restricted manner, but did not cross‐react with GM2, GD2, or lactosylceramide. This indicated that the T‐cell receptors reacting with GD3 recognize glucose‐galactose linked to at least one N‐acetyl‐neuraminic acid but will not accommodate a terminal N‐acetylgalactosamine. Immunization with GM2, GM3, GD2, or lactosylceramide did not induce an NKT‐cell response. Coimmunization of GM3‐loaded antigen‐presenting cells (APCs) with GD3‐loaded APCs suppressed the NKT‐cell response to GD3 in a CD1d‐restricted manner. This suppressive effect was specific for GM3 and was a local effect lasting 2–4 days. In vitro, GM3‐loaded APCs also suppressed the interleukin‐4 response, but not the interferon‐γ response, of NKT cells to α‐galactosylceramide. However, there was no effect on the T helper type 2 responses of conventional T cells. We found that this suppression was not mediated by soluble factors. We hypothesize that GM3 induces changes to the APC that lead to suppression of T helper type 2‐like NKT‐cell responses.
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