What structures are seen by a T cell in the immune response to a lupus autoantigen?

In this decade we have witnessed substantive progress in solving a number of the fundamental enigmas in systemic lupus erythematosus (SLE) that thwart progress towards achieving the goal of inducing disease remission in all patients with this challenging disease. This issue of the Annals of the Rheumatic Diseases contains a paper by Zhao et al 1 , ‘Nature of T cell epitopes in lupus antigens and HLA-DR determines autoantibody initiation and diversification’, which greatly advances understanding of four critical aspects of SLE that are included among these enigmas: Why is the susceptibility to develop SLE associated with the Major Histocompatibility class II allele desinated  HLA-DR3? What role does the recognition by specific T cell clones of self-peptides presented by HLA-DR3 molecules play in the process of epitope spreading that drives the progressive intensification of a seemingly inconsequential autoimmune response to become a virulent life-threatening autoimmune disease? What roles do the peptides of the diverse commensal and environmental antigens of a person’s environment play in this progressive intensification? Lastly, what events are involved in the transition from asymptomatic autoimmunity to the heterogeneous organ involvement of clinical disease? The paper addresses these questions by analysing in detail the characteristics of both the B cell and T cell immune response to Smith antigen (Sm). It especially focuses on the particular peptides recognised by the clonally specific T cell receptors (TCRs) of the T cell clones proliferating in HLA-DR3 transgenic mice during the response to immunisation by Sm, by elegantly exploiting the property of murine T cells to be readily immortalised as hybridomas.Several intriguing findings in this paper that address …