Full-back Robbie Henshaw and inside centre Stuart Olding will make their debuts for Ireland in Saturday's Test against the United States in Houston.
Three other players - fly-half Ian Madigan, prop David Kilcoyne and flanker Iain Henderson - will start for Ireland for the first time having previously been capped off the bench.
There are a further three uncapped players among the replacements with forwards Mike Sherry, Jamie Hagan and Tommy O'Donnell all included.
Mike Ross is the most capped player in the selected team and he packs down in the front row with Richardt Strauss and Kilcoyne.
Mike McCarthy and Devin Toner form the second row pairing with Henderson and Chris Henry on either side of Ireland's summer tour captain Peter O'Mahony in the back row.
Speaking ahead of the game, interim head coach Les Kiss said: "We've had a good week of preparation and the players have settled well in Houston.
"This is a young team with five players starting for the first time and we are under no illusions as to the challenge posed by an experienced and improving USA Eagles team."
Ireland: 15 Robbie Henshaw, 14 Fergus McFadden, 13 Darren Cave, 12 Stuart Olding, 11 Simon Zebo, 10 Ian Madigan, 9 Isaac Boss, 8 Peter O'Mahony (c), 7 Chris Henry, 6 Iain Henderson, 5 Devin Toner, 4 Mike McCarthy, 3 Mike Ross, 2 Richardt Strauss, 1 David Kilcoyne.
Replacements: 16 Mike Sherry, 17 Jamie Hagan, 18 Tom Court, 19 Dan Tuohy, 20 Tommy O'Donnell, 21 Paul Marshall, 22 Paddy Jackson, 23 Felix Jones.
Date: Saturday, June 8
Venue: BBVA Compass Stadium, Houston
Kick-off: 19.30 (local)
Referee: Francisco Pastrana (Argentina)
Assistant referees: Bryan Arciero (Canada), Chris Assmus (Canada)
Assessor:: Clayton Thomas