Incomplete T-cell tolerance and epitope-specific responses to the NR1 subunit in NMDA receptor antibody-associated encephalitis.

NMDA receptor antibody-associated (NMDAR-Ab) encephalitis primarily affects young women and children and often requires prolonged intensive care admission. Currently available first- and second-line therapies are effective, but patients can be refractory and residual deficits are not uncommon. Although B-cell lineages and specific NMDAR (NR1 subunit) antibodies have been examined in detail, the subtypes and roles of antigen-specific T cells in providing T-cell help to drive the IgG antibody response, cytotoxic effects or other roles have not been reported. Peripheral blood mononuclear cells from eight patients and eight healthy volunteers underwent three rounds of stimulation with pooled 15-mer peptides spanning the length of the NR1 sequence. At each round of stimulation, functional CD4+ and CD8+ T-cell responses to NR1-derived peptide pools were assessed using flow cytometry. CD4+ and CD8+ T responses to NR1-derived peptide pools were identified in both patients and healthy volunteers. Patient CD4+ T-cell responses were more frequent compared to healthy volunteers after the first round of stimulation, with fewer responses after the third round. Healthy volunteer CD4+ T cells showed the opposite trend (