Shane Jennings will make his Ireland debut alongside Leo Cullen and Geordan Murphy against Marcelo Loffreda's Argentina in Buenos Aires this Saturday (kick-off 8.10pm BST).
Jennings and Cullen, who will move to Leinster this summer, are named at openside flanker and lock, while Murphy starts at full back.
All three players were instrumental in Tigers' double-winning season and will now be looking to secure a place in Ireland's World Cup squad.
Ireland, who narrowly missed out on an away victory over their World Cup group opponents last weekend, have made wholesale changes from the first Test, with only four players retaining their places in the starting XV.
Ireland: G Murphy; B Carney, B Murphy, G Duffy, R Kearney; J Staunton, E Reddan; B Young, F Sheahan. S Best, capt, L Cullen, M O'Driscoll, A Quinlan, S Jennings, S Ferris.
Replacements: B Jackman, T Buckley, M O'Kelly, N Best, I Boss, K Lewis, L Fitzgerald.
Jennings and Cullen, who will move to Leinster this summer, are named at openside flanker and lock, while Murphy starts at full back.
All three players were instrumental in Tigers' double-winning season and will now be looking to secure a place in Ireland's World Cup squad.
Ireland, who narrowly missed out on an away victory over their World Cup group opponents last weekend, have made wholesale changes from the first Test, with only four players retaining their places in the starting XV.
Ireland: G Murphy; B Carney, B Murphy, G Duffy, R Kearney; J Staunton, E Reddan; B Young, F Sheahan. S Best, capt, L Cullen, M O'Driscoll, A Quinlan, S Jennings, S Ferris.
Replacements: B Jackman, T Buckley, M O'Kelly, N Best, I Boss, K Lewis, L Fitzgerald.