The function of CTLA4 in suppressing IL-2 production has been long established (Krummel and Allison, 1996), but our results demonstrate that this checkpoint is genetically variable in the physiologically relevant range of IL-2 suppression in humans, suggesting a mechanistic explanation for association of the CTLA4 variant with rheumatoid arthritis. Here, CTLA4 is linked to rheumatoid arthritis.