My dad was born at Fontana and my grandparents are from Bryson city so I've spent a lot of time in that area.
Not sure where you are going at Santeelah, but based on the 19s-28-43-129 route I will assume Robinsville.
You can take your rig on that route but I do not think it is ideal. There are curves and ups and downs, but nothing out of the ordinary for the Smokeys. As
you leave Bryson City, 19/64 is a relatively new 4 lane. On the route you describe, you would be getting off 19/74 where 19/74 goes to a 2 lane. HOWEVER, if you stay on 19/64 and continue thru Nantahala Gorge (a beautiful drive in itself in the fall), then when you come out of the Gorge at Topton you can turn right onto the same 129 you were headed for. I believe this would be easier and perhaps more scenic. At the very least it is shorter and less tedious.
The caveat is that you CAN NOT take your rig on Highway 129 north into Tennessee past Topoco. That starts a stretch of that road known to motorcyclists as "the Dragon", and people ship their motorcycles here from literally all over the world to make that 10 mile run. You can google The Dragon and see disaster pictures of 18 wheelers that tried to go thru that route.
You CAN make a large loop via 28 and 129 as they connect at Fontana without going on the Dragon. There is a small campground at Fontana Dam, along with a 14% grade that is about a mile long between the village and the campground. This would be a pretty drive with your tow vehicle solo. Fontana Resort/lake/dam is spectacular in the fall.
As to Newfound Gap, I've made that trip dozens of times but never with our trailer. The NC side has probably 15 miles of 7-8% steady grade. However, my reluctance is around not knowing the park rules on campers. Years ago 18 wheelers could only travel that route at night and today they are banned all together. My only suggestion would be to confirm with the park service that RV's are allowed and if there are size restrictions.
