Stimulation with cit-H3 induced ACPA+ RA CD8+ T cells to express cytotoxic mediators and blockade of CD8 or the HLA class I complex inhibited this response (Supplementary Fig. 16), demonstrating activation of anti-cit-H3 CD8+ T cells is also dependent on HLA class I presentation of cit-H3. This evidence concerns the gene CD8A and rheumatoid arthritis.