Electronic Poster | Session 2

028 – Identification and epitope mapping of autoreactive T cells against the dopamine-2 receptor in paediatric movement and psychiatric disorders

Deepti Pilli (1) – Ganesha Liyanage (1) – Deborah Lin (1) – Chelsea B. Bassett (1) – Fiona Tea (1) – Fiona Lee (1) – Vera Merheb (1) – Alicia Zou (1) – Joseph A. Lopez (1) – Anthony D. Kelleher (2) – Russell C. Dale (1) – Fabienne Brilot (1)
Brain Autoimmunity Lab, Kids Neuroscience Centre, Kids Research, The Children’s Hospital at Westmead, Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, Australia (1) – The Kirby Institute for Infection and Immunity in Society, University of New South Wales/St Vincent’s Hospital, Sydney, Australia (2)

Introduction: Autoimmunity is a recognised cause in a distinct and treatable subgroup of patients with movement and psychiatric disorders (MPD). This is largely supported by studies of autoantibodies against neuronal proteins that are crucial for neurotransmission, such as the dopamine-2 receptor (D2R). However, the role of T cells in these diseases remains unknown. As T cells are a prominent cell subset in the immune network, we aimed to identify and characterise D2R-specific T cells in MPD. Method: Peripheral blood and PBMCs were collected from paediatric patients with MPD (n=23). These samples were cultured and stimulated with a library of human D2R peptides and the frequency of rare activated D2R-specific CD4+ T cells were quantified by the co-expression of CD25 and CD134. Anti-D2R antibody sero-positivity was established using a flow cytometry live cell-based assay. Results: 9/23 MPD patients had a higher frequency of activated CD25+CD134+CD4+ T cells than controls in response to D2R peptides. In these 9 patients, the immunodominant peptide pools corresponded to aa121-155 (4/9), aa156-195 (3/9), and aa381-443 (5/9). Deconvolution of these pools suggested that the T cell epitopes lie within regions aa121-145, aa171-195, and aa396-430. Interestingly, there was no difference in the frequency of total CD4+ T cells and CD39+CD4+ Treg cells in patients compared to controls (p<0.05). Patients with D2R-specific T cells were sero-negative for anti-D2R antibodies. Conclusion: Activated D2R-specific CD4+ T cells were detected in a subgroup of paediatric patients with MPD. Notably, they were detected independent of anti-D2R antibodies, suggesting that autoreactive T cells may play a dominant role and define a distinct subgroup of MPD. As with autoantibodies, identification of autoreactive T cells can improve the diagnosis and prognosis of MPD, especially in patients initially classified as idiopathic.