Autoreactive CD4⁺ and CD8⁺ T-cell responses are HLA restricted. CFSE-based proliferation assays were performed on PBMC specimens from untreated patients with MS in the presence of anti-HLA antibodies or appropriate control immunoglobulin. The dot plots demonstrate CD4⁺ and CD8⁺ MOG-specific proliferative responses from one of the patients in the presence of the indicated antibodies. The 2 left panels demonstrate the effect of HLA class I blockade (compared with the IgG1 control), whereas the 2 right panels demonstrate the effect of HLA class II blockade (compared with IgG2a control). CFSE staining is shown on the x-axis and CD8 staining on the y-axis. The numbers represent the proliferating fraction of CD4⁺ (black) and CD8⁺ (dark gray) T cells. Anti-class I antibodies predominantly blocked CD8⁺ T-cell proliferation but also diminished CD4⁺ proliferation. Anti-class II antibodies had a predominant effect on CD4⁺ T-cell proliferation but also diminished CD8⁺ proliferation. These results are representative of HLA blockade data from 35 distinct CD4⁺ and CD8⁺ proliferative responses from 13 patients with MS responding to several different neuroantigenic peptide pools (MBP, PLP, MOG, MAG, OMGP, and MOBP).