The letter that comes next in the sequence O, T, T, F, F, is S. Each letter represents the first letter of each number in the sequence of natural numbers. S stands for "Six."
The sequence "O, T, T, F, F" and similar phrases, such as "O, T, T, F, F, S, S," are mentioned on a variety of brain teaser and trivia sites, such as Chaos Trivia, Braingle and others. The phrase contains the first letter of each natural number: "One, Two, Three, Four, Five." Therefore, the next several terms in the numeric sequence are: "Six, Seven, Eight, Nine, Ten." Based on the nature of the riddle, this is written out as: "O, T, T, F, F, S, S ,E, N, T" and so on.