Ulster players Robert Baloucoune, James Hume, Tom O'Toole and Nick Timoney will make their Ireland debuts in Saturday's summer Test against the USA in Dublin.
Munster pair Craig Casey and Gavin Coombes, plus Leinster second row Ryan Baird, are handed their first starts, while four uncapped players are chosen among the replacements for the game.
Harry Byrne, Caolin Blade, Paul Boyle and Fineen Wycherley could make their bows if called upon from the bench.
James Ryan is again named as captain.
Head coach Andy Farrell makes a total of seven changes to the starting team that defeated Japan 39-31 in a thrilling encounter at the Aviva Stadium last weekend.
Of the four starting debutants, O'Toole and Timoney will play at tight-head prop and open-side flanker respectively, with Baloucoune on the right wing and Hume at outside centre.
Full-back Hugo Keenan starts his 13th consecutive game for Ireland against Gary Gold's Eagles.
In the back row, Caelan Doris switches to the blindside flank to accommodate Gavin Coombes' maiden starting appearance at number eight.
Ireland revealed on Monday that Chris Farrell and Jordan Larmour had been released from the Ireland camp with a head injury and a groin problem respectively.
Back row Peter O'Mahony also left the squad to begin his off season.
The US lost 43-29 to England at Twickenham last week.
Ireland have played the US twice in the past three years, winning 55-19 in New Jersey in 2017 and then 57-14 in Dublin in 2018.
The teams will meet again in Las Vegas in the autumn.
Ireland: Keenan; Baloucoune, Hume, McCloskey, Conway; Carbery, Casey; Kilcoyne, Kelleher, O'Toole; Baird, Ja Ryan (capt); Doris, Timoney, Coombes
Replacements: Heffernan, E Byrne, Bealham, Wycherley, Boyle, Blade, H Byrne, Addison.