Sale prop Bevan Rodd and Newcastle hooker Jamie Blamire start in a rookie England front row for Saturday's Test with world champions South Africa.
Prop Joe Marler, who will not train until Friday after isolating with Covid-19, is named on the bench, as is uncapped hooker Nic Dolly.
Joe Marchant is on the wing with Manu Tuilagi returning to the midfield.
Flanker Courtney Lawes captains the side at Twickenham in the absence of the injured Owen Farrell.
England's last meeting with South Africa was the 2019 World Cup final in which the Springbok pack dominated to claim a 32-12 win.
Ex-British and Irish Lions prop Alex Corbisiero said during the week that England would face an "uphill battle" against the world champions without the experience of Jamie George.
So Rodd, receiving his second cap, and Blamire, gaining his fifth, face a tough Test at Twickenham, with prop Kyle Sinckler offering more international expertise in the front row.
Jamie George's injury offers 23-year-old Blamire the chance to continue a remarkable England journey that has seen him score six tries in four games, having only ever started three times previously for club Newcastle.
England's scrum will be propped up by six forwards on the bench, with number eights Alex Dombrandt and Sam Simmonds both named once again.
In the backs, centre Marchant is selected on the wing ahead of Max Malins, with Adam Radwan left out of the matchday squad.
Fly-half Marcus Smith starts for the second week in a row and this time will partner Tuilagi in midfield, with Henry Slade at outside centre.
England have claimed convincing wins against Tonga and Australia so far this autumn, but Eddie Jones said Saturday's match will be the side's "biggest game of the season".
"We want to finish with a bang," he continued.
"We've been really pleased with the preparation this week and how the team has continued to develop over the past month.
"Now we want to put on our best performance this autumn in front of a capacity 82,000 crowd at Twickenham."
England: Steward; Marchant, Slade, Tuilagi, May; Smith, Youngs; Rodd, Blamire, Sinckler, Itoje, Hill, Lawes (capt), Underhill, Curry.
Replacements: Dolly, Marler, Stuart, Ewels, Simmonds, Dombrandt, Quirke, Malins.
Phone: (800) 737. 6040
Fax: (800) 825 5558
Website: 
Email: 
