Jessie and James are battled four times in Pokemon Yellow, where they are collectively referred to as "Rocket". They are also battled five times in the Let's Go games, where they are distinguished by their actual names.
James (Bulbapedia)
You actually can face off against Jessie and James in the games, in pokemon yellow. However, they refer to them as "rocket" without actually revealing their name. But the fact that they use remarkably similar sprites, and that they have an Ekans, Meowth, and Koffing is a strong reference to the series.
http://www.youtube.com/watch?v=g_MMFXRwb2w
Note how they say "surrender now or prepare to fight" before battling, and Team rocket blast off at the speed of light" at the end.