To determine whether autoimmune disease risk or protective HLA-DRB1 alleles have distinct effects on macrophage polarization we first studied ex vivo primary bone marrow-derived macrophages (BMDMs) isolated from transgenic mice43,44 that express human HLA-DRβ chains coded by the DRB1*04:02 allele with a PE (70-DERAA-74) sequence in the TAHR (“PE Tg”), versus BMDMs from mice of the same genetic background expressing a SE (70-QKRAA-74) sequence, encoded by the RA-susceptibility allele DRB1*04:01 (“SE Tg”). The gene discussed is HLA-DRB1; the disease is rheumatoid arthritis.