Self-reactive human CD4 T cell clones form unusual immunological synapses

Abstract

Compared with influenza-specific T cells, self-reactive T cells from patients with multiple sclerosis or type 1 diabetes fail to slow down and do not form normal immunological synapses upon encounter with cognate self-peptide presented by MHC.

Dendritic Cell–Dependent In Vivo Generation of Autoregulatory T Cells by Antidiabetogenic MHC Class II

“…In addition, structural studies have shown that, as compared with foreign Ag-specific TCRs, autoreactive T cells tend to either bind their cognate pMHC ligands with a unique topology or to recognize a peptide that occupies only part of the peptide binding site of the presenting MHC molecule (61). These TCRs make fewer contacts with peptide residues (61) and appear to catalyze the formation of unconventional synapse structures as compared with foreign Ag-specific TCRs (62). Such an altered mode of binding may account for the MHC promiscuity of certain autoreactive TCRs, whereby polymorphic MHC residues on other (nonselecting) MHC molecules would compensate for the paucity of molecular contacts with the selecting pMHC complex(es).…”

Autoreactive T cells in type 1 diabetes

“…Ultimately, differences in HLA-peptide complex interactions can impact responding T cell activation and phenotypes and synergize with the reduced insulin expression in the thymus that is associated with predisposing insulin gene variants. Moreover, CD4 + T cells from T1D patients display abnormal immunological synapsis associated with escape from negative selection and enhanced effector responses upon encounter with cognate antigen (172).…”

Plasma membrane-associated superstructure: Have we overlooked a new type of organelle in eukaryotic cells?

“…In Drosophila depletion of focal adhesion proteins in glial cells, disrupts photoreceptor axon migration in the visual system of these flies (Xie et al, 2014). Human self-reactive CD4 T cells from autoimmune obtained from patients with multiple sclerosis and type 1 diabetes display unusual T cell immunological synapses, compatible with the possibility that alterations in these synapses could be involved in the development of autoimmunity (Schubert et al, 2012). Alterations in molecular components or the signaling at the postsynaptic densities, including synaptic receptors and channels, scaffolding and adaptor proteins and enzymes, associate to the development of Alzheimer´s disease and other dementias (Gardoni, 2008;Gong and Lippa, 2010).…”