We rigorously assessed T cell responses in patients with SLE after BNT162b2 vaccination using spheromers specific for Spike protein epitopes bound to either HLA-A*02:01 or DRB*15:01 (24) to identify MHC Class I– or MHC Class II–restricted T cells and detected a consistently reduced induction of SARS-CoV-2 Spike–specific CD8+ and CD4+ T cells. Here, HLA-A is linked to systemic lupus erythematosus.