The use of prefixes actually predates their recognition as security enhancements implemented in 1869 on original series notes. Here's the story created with much help from Huntoon... The treasury sheet SNs and seals were overprinted on Original Series notes at the forerunner to the BEP at the Treasury Dept. Building in Washington. Bank sheet SNs were printed by the bank note companies prior to delivery to the Treasury Dept. Once the first million serials were consumed, treasury switched from red to blue numbers. A prefix letter was used beginning with the 3rd million, or as early as January 1865 for $5-$5-$5-$5 sheets. Treasury sheet SNs as security devices was examined in April 1869 and there were 3 changes implemented. (1) In most cases, prefix letters were added to the numbers if they were not already in use for that plate combination. [exceptions were 50-100 (see pic), 4x$500 and 4x$1000] (2) numbers were terminated with brackets (but see pic--I would call it a parenthesis) (3) spaces between prefix letters and numbers were eliminated. Estimated 1st secured numbers: 5-5-5-5 E225978, 10-10-10-20 A61264, 50-100 245090, 1-1-1-2 B556082.

I collected a few examples for the sheets listed above, both before and after implementation of the security enhancements. The interesting one to me is for the 10-10-10-20 for Raleigh (1682) $10 SN A77519 (that's the earliest note with an A prefix that I could find). It's a great note with a rare Jeffries-Spinner Treasury signature combination found on original series notes.  It sports those security enhancements although that number is just a bit crooked if I'm allowed to be critical of this awesome note!