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That Agents of SHIELD. ties into the Marvel Cinematic Universe is a given; it’s a spin-off from those movies, after all, led by a character who first appeared in Iron Man.
However, these links are generally dictated by the MCU. Season 1 had the major, game-changing tie-in to Captain America: The Winter Solider, which really kick-started the show, and season 2 had a less significant connection to Avengers: Age of Ultron.
