Compartmentalization of adaptive immune cells into T and B cells is not absolute and violators of this paradigm are likely key drivers of autoimmune diseases
"X" Cell
A new study from Hamad’s lab published in Cell describes a previously unknown lymphocyte that is a dual expresser (DE) of TCR and BCR and key lineage markers of B and T cells (also known as an “X” Cell for its crossover phenotype). In type 1 diabetes (T1D), DEs are predominated by one clonotype that encodes a potent CD4 T cell autoantigen in its antigen binding site (referred to as x-idiotype). Molecular dynamics simulations revealed that the x-idiotype peptide (x-Id) has an optimal binding register for diabetogenic HLA-DQ8. In concordance, synthesized x-Id peptide forms stable DQ8 complexes and potently stimulates autoreactive CD4 T cells from T1D, but not healthy controls. Moreover, x-clonotype-bearing mAbs are autoreactive against CD4 T cells and inhibit insulin-tetramer binding to CD4 T cells. Thus, compartmentalization of adaptive immune cells into T and B cells is not absolute and violators of this paradigm are likely key drivers of autoimmune diseases.