As CD4+ T cell responses are generally stronger when epitopes are presented by HLA-DR vs. HLA-DQ23, HLA-DRB1*04 responses to the p.S129 unphosphorylated form of α-synuclein could be dominant in individuals with HLA-DRB1*04, explaining the protective effect of this HLA subtype in PD. This evidence concerns the gene HLA-DRB1 and Parkinson disease.