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A "hotspot" for autoimmune T cells in type 1 diabetes
#MMPMID27183386
Stadinski BD
; Obst R
; Huseby ES
J Clin Invest
2016[Jun]; 126
(6
): 2040-2
PMID27183386
show ga
The ability of a single T cell antigen receptor (TCR) to cross-react with
multiple antigens allows the finite number of T cells within an organism to
respond to the compendium of pathogen challenges faced during a lifetime.
Effective immune surveillance, however, comes at a price. TCR cross-reactivity
can allow molecular mimics to spuriously activate autoimmune T cells; it also
underlies T cell rejection of organ transplants and drives graft-versus-host
disease. In this issue of the JCI, Cole and colleagues provide insight into how
an insulin-reactive T cell cross-reacts with pathogen-derived antigens by
focusing on a limited portion of the peptides to provide a hotspot for binding.
These findings dovetail with recent studies of alloreactive and autoimmune TCRs
and suggest that the biochemical principles that govern conventional
protein-protein interactions may allow the specificity and cross-reactivity
profiles of T cells to be predicted.
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