The long pointy Opentop firing pins that used to pierce primers should be a thing of the past. Some years back Uberti went with a more conical shape, similar to the replacements from Happy Trails. But they should be plenty long if they haven't been messed with. How old is this OT? As Montana Slim mentioned, if this had the old pointy FP maybe somebody filed it down? One of my '51 conversions had this issue (different FP style, but still sharp), the 'smith went a bit far when dulling it to prevent primer piercing. Worked great for 10 years, then started getting the occasional misfire depending on how deeply the primer was seated, so I replaced it (had to dull the new one a bit as well).
Be sure the top end of the mainspring isn't hitting the frame when cocked, nor rubbing the side of the frame (mounted a bit off center). You can see this by working the action with the grips off.
Make sure the hammer isn't rubbing the side of the frame opening. Scrape marks on the side would indicate this, as well as feel. Measure the headspace. That would be the distance between the cartridge rim and the recoil shield where the firing pin hole is. And measure how much firing pin protrusion you have through the FP hole with hammer down. I'm not sure what those values should be, but Pettifogger and Coffinmaker will know. And is there much or any endshake (cylinder can move front to back)?
CCI primers are the hardest to set off, Winchester medium, and Federals are the softest. Factory springs should set them all off, but if you are getting misfires with Federals then something is seriously wrong! Also, be sure the ammo does not have any high primers, as this will cause a misfire. Usually the first hammer fall will seat the primer, then trying it again will fire. Since both your buddy's ammo and your primed cases had the problems, I would tend to doubt high primers, but couldn't hurt to check.
Another thing that can cause misfires is the cylinder over-rotating and causing off-center primer hits (or miss it altogether). This usually only happens with fast cocking, and can be verified by looking at the primer after the misfire. If you do get a misfire, check to see if the hit on the primer is as deep as ones that go off. Also do these rounds go off with a second hit?