For the Jacksonville Jaguars, the path to AFC legitimacy always has run through Tom Brady.

The Jaguars are the only AFC team never to defeat the New England Patriots quarterback in his 19-year career, now 0-8 (including the playoffs) against him. That slide almost came to an end in last season's AFC Championship Game, but Brady engineered a comeback from a 10-point fourth-quarter deficit to power the Patriots back to the Super Bowl.

With a loaded defense returning and the Patriots navigating a handful of offensive changes, Jacksonville has its best shot yet at toppling Brady when it hosts New England on Sunday. But doing so will still require a confluence of events tilting in the Jaguars' favor.

The most intriguing showdown with the game is unquestionably Jalen Ramsey's impending faceoff with Rob Gronkowski after the Jaguars cornerback ridiculed the Patriots tight end in the offseason. And while Ramsey said that Gronkowski would have to line up against him, the Jaguars might use a variety of players — including linebackers Myles Jack and Telvin Smith and safeties Tashaun Gipson and Barry Church — to counter the four-time all-pro.

But even as the acknowledged focal point of the Patriots' passing attack, Gronkowski poses a special problem for Jacksonville given Brady's willingness to throw to him even in double coverage.

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With New England's wide receivers recording just nine catches last week, it seems unlikely Brady will test the Jaguars often on the outside. While running backs James White and Rex Burkhead should be frequent targets working underneath, the Jaguars' linebacker tandem of Jack and Smith might be the league's best equipped duo to handle such an assignment.

Brady will also have to deploy a quick trigger against a potent Jacksonville pass rush that looks to have an advantage against the Patriots' offensive front. While left tackle Trent Brown has fared well in the early going, defensive end Yannick Ngakoue's speed off the edge could prove difficult for the 6-8, 380-pounder to handle.

Here are four other matchups that will shape Week 2:

Panthers RB Christian McCaffrey vs. Falcons' linebackers

Perhaps no two teams were more ravaged by injuries in the first week than the Panthers and Falcons. Carolina now has both of its starting tackles (Matt Kalil and Daryl Williams) on injured reserve and will be without Pro Bowl guard Trai Turner (concussion) and tight end Greg Olsen (fractured foot). Atlanta, meanwhile, lost safety Keanu Neal (torn ACL) and linebacker Deion Jones (foot injury) after its season opener.

The Panthers' losses would seem to shift a heavier burden on McCaffrey, especially against the Falcons. Ron Rivera said this week he hoped to have the second-year running back get 15 to 20 carries and six to 10 catches every game. But with the loss of Olsen and Norv Turner continuing to emphasize a quick-passing attack for Cam Newton, he could take on a heavier workload as a receiver.

That could spell trouble for the Falcons, who relied heavily on Jones and Neal to handle running backs in coverage and chase them down when the defense concedes short throws underneath. Linebacker Duke Riley will have to pick up some of the slack for Jones, while fill-in safety Damontae Kazee will also play a prominent role.

Packers' receivers vs. Vikings' secondary

All eyes are on Aaron Rodgers as the two-time MVP enters a key rivalry game listed as questionable with a knee injury following his Week 1 heroics against the Bears. But even if Rodgers does get his chance for revenge against the same Vikings team that cracked his collarbone last season, his receivers will have to do their part against last season's top-ranked defense.

Rodgers and the Packers found success against the Bears when they neutralized the pass rush by going to quick-hit connections. A similar strategy might be necessary against the Vikings given the threat of defensive ends Everson Griffen and Danielle Hunter. And with top pass catcher Davante Adams listed as questionable with a shoulder injury, Green Bay will likely need at least one of its rookie targets (J'Mon Moore, Marquez Valdes-Scantling and Equanimeous St. Brown) to step up and assist Randall Cobb and Geronimo Allison.

Minnesota's defense, however, allowed the fewest yards after catch of any group in 2017 and offers few easy answers for any opponent. The best course of action for the Packers might be attacking Mackensie Alexander and rookie Mike Hughes in the slot. But even that can be dangerous, as Hughes returned an interception 28 yards for a touchdown last week against the 49ers.

Cowboys offensive line vs. Giants DT Damon Harrison

Dallas' long-gestating issues in the passing game were on full display last week, as Dak Prescott was unable to click with a new receiving corps. For the foreseeable future, the Cowboys and their opponents know an incontrovertible truth: This offense is fully Ezekiel Elliott's show.

But there's a 341-pound problem awaiting Elliott at the middle of the Giants' defense in Harrison. With New York's defense shifting to a 3-4 under new coach Pat Shurmur and coordinator James Bettcher, "Snacks" has remained a stabilizing run presence. His ability to clog lanes and create a push up front was already on display last week against the Jaguars, who had the NFL's top rushing attack last year but wouldn't have cracked the 100-yard mark if not for a 41-yard keeper by quarterback Blake Bortles.

Center Joe Looney, filling in for the still-sidelined Travis Frederick, will need plenty of help from right guard Zack Martin on double teams. Still, the Cowboys might have to focus on attacking the edges of Giants' defense.

Steelers RB James Conner vs. Chiefs' front seven

With Le'Veon Bell still away, Pittsburgh once again turns to Conner as the focus of its run game. And though the Chiefs might be relieved at not having to face a two-time all-pro who has torn them apart in the past (Bell has averaged 126.8 rushing yards in four regular-season games against Kansas City and logged 170 rushing yards in a divisional playoff win in 2017), the second-year running back could still pose significant problems.

Conner looked comfortable in the lead role in the opener, logging 192 yards from scrimmage and two touchdowns on 36 touches against the Browns. With quarterback Ben Roethlisberger dealing with an elbow injury, Conner should once again see a heavy volume of carries as Pittsburgh tries to keep its defense rested and off the field against Kansas City's supercharged attack.

The Chiefs ranked just 25th against the run last season but now have two downhill hitters on the inside in linebackers Reggie Ragland and Anthony Hitchens. One area of concern, however, could be stopping Conner in the passing game after Kansas City's defense gave up 189 receiving yards to Chargers running backs Melvin Gordon and Austin Ekeler last week.

Follow Michael Middlehurst-Schwartz on Twitter @MikeMSchwartz.