Vitamin B12 and 5-methyl-tetrahydrofolate (THF) interact to produce methionine for T cell activation. Methionine synthase is a vitamin B12-dependent enzyme that produces methionine via homocysteine and 5-methyl-THF. The uptake of methionine is required in T-cells to provide methyl groups to RNA and DNA, needed for the cells to proliferate and differentiate. The absence of methionine leads to the failure of T-cell expansion and a weakened cell-mediated immune response. Methionine is essential to synthesize S-adenosylmethionine (SAM), which plays a major role in transmethylation reactions that support immune function. Lymphocytes depend upon SAM in activated states for transmethylation events involving DNA, RNA, or protein molecules, which are required for maintaining cell function.