Prevention of T cell activation by interference of internalized intravenous immunoglobulin (IVIg) with MHC II-dependent native antigen presentation

Activation of self-reactive CD4+ T cells plays a central role in the initiation and maintenance of autoimmune diseases. We recently reported that intravenous immunoglobulin (IVIg) inhibits the MHC II-restricted CD4+ T cell activation induced by the presentation of immune complexes. Because native antigens can also play a role in the induction of several autoimmune diseases, we determined whether IVIg could also affect CD4+ T cell activation following presentation of native antigens by APCs. Here we report that IVIg significantly reduces the activation of CD4+ T cells by native ovalbumin. The inhibitory effect is FcγR-independent and occurs following internalization of IVIg inside APCs, where it interferes with the intracellular events leading to MHC II-dependent antigen presentation. The effect of IVIg on native antigen presentation could therefore contribute to dampen the autoimmune reaction by reducing CD4+ T cell activation and the subsequent inflammatory response induced by these cells.

► We show that IVIg reduces the activation of helper T cells by native antigens.
► APC, but not T cells, are a direct target of IVIg.
► IVIg decreases the amount of I-A-peptide complexes presented by APC to T cells.
► This reduction correlates with IVIg internalization in APC.
► This effect represents a new mechanism for the anti-inflammatory activity of IVIg.