22 personnel means that there are two running backs, two tight ends, and one receiver on the field. With bigger offensive players on the field and a more run-focused personnel grouping, defenses are likely to match with big personnel themselves. 22 personnel is often used in short-yardage situations. The two tight ends can offer mismatches either in run blocking or on passes against the bigger linebackers that the defense brings in.
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The tight end matchup can be a huge advantage. If they are a positive player in run blocking, offenses can use them to add an extra gap to be defended. That forces the defense to make a choice on who they bring in to combat that. Do they bring in a heavier linebacker to match the physicality of the blocking, or do they stay with a Nickel player that can cover better in the pass game, but is at a clear disadvantage against the tight end in run blocking. The same can be said for the additional running back. They can be used for misdirection, as a lead blocker, or to create a mismatch in the passing game.