That trimming capacitor on the Iss5 is actually to trim the 8302's 'real-time' clock

I do think that timing tolerances between Minerva and Tk2 could well be a significant factor, but again - this wouldn't in itself explain why different types of high-level device access (OPEN, LOAD vs. LBYTES) show different behaviour - the very same _physical_ code is used in each case.
Assuming my hardware isn't flaky, a more likely explanation could be that, as Tk2 was written before Minerva and would have been designed against original QDOS 'conventions'; Tk2 would be assuming register usage and other environmental factors that are no longer the same under Minerva. I've seen several examples of older toolkits behaving differently under QDOS vs Minerva, as Minerva tries to follow the official documentation, which QDOS often didn't!
But Derek's observation would seem to indicate that Minerva + Tk2 networking worked OK...
I should point out that I've made some significant hardware mods to both Issue boards and, on the Iss5 in particular, I have extended the memory by also shadowing the internal QL DRAM: writes go to both DRAM and fast SRAM in the lower 64kB - necessarily contended and which includes the video RAM range, whereas all reads come from the fast SRAM across the entire RAM memory map - or as much as I've filled with the 512k SRAm IC - and is uncontended (zero-ws). Everything else seems to work nicely and some simple tests show a significant 'speed' increase, though not the full 2x, as any real-world test will write as well as read from the lower memory (only reads are faster in that lower 64kB).
Another reason I don't think the different hardware/Issue boards are the root-cause is that the behaviour is symmetric between them - whichever has Tk2 running will fail to respond to the scout/header when LBYTES is used.
In my earlier testing, I also tried a few different 8302 and 8301 IC combinations as well - didn't seem to show any difference in behaviour.
Its a bit of a distraction from my USB-QNet project, but I will continue to try to code-in the Minerva physical routines in to the Tk2 networking code.