On one side is Harvard, the nation’s oldest and wealthiest university, with a brand so powerful that its name is synonymous with prestige. On the other side is the Trump administration, determined to go farther than any other White House to reshape American higher education.

Both sides are digging in for a clash that could test the limits of the government’s power and the independence that has made U.S. universities a destination for scholars around the world.

On Monday, Harvard become the first university to openly defy the Trump administration as it demands sweeping changes to limit activism on campus. The university frames the government’s demands as a threat not only to the Ivy League school but to the autonomy that the Supreme Court has long granted American universities.

“The university will not surrender its independence or relinquish its constitutional rights,” the university’s lawyers wrote Monday to the government. “Neither Harvard nor any other private university can allow itself to be taken over by the federal government.”

The federal government says it’s freezing more than $2.2 billion in grants and $60 million in contracts to Harvard. The hold on funding marks the seventh time the Trump administration has taken such a step at one of the nation’s most elite colleges, in an attempt to force compliance with Trump’s political agenda. Six of the seven schools are in the Ivy League.

No university is better positioned to put up a fight than Harvard, whose $53 billion endowment is the largest in the nation. But like other major universities, Harvard also depends on the federal funding that fuels its scientific and medical research. It’s unclear how long Harvard could continue without the frozen money.

Already, Harvard’s refusal appears to be emboldening other institutions.

After initially agreeing to several demands from the Trump administration, Columbia University’s acting president took a more defiant tone in a campus message Monday, saying some of the demands “are not subject to negotiation.”

In her statement, Claire Shipman said she read of Harvard’s rejection with “great interest.”

“Harvard is obviously a particularly powerful institution. And its decision has potential to galvanize other universities into some kind of collective pushback,” said David Pozen, a Columbia law professor who argued that the government’s demands are unlawful.

Ultimately, the conflict could be settled in federal court. A faculty group has already brought a legal challenge against the demands, and many in academia expect Harvard to bring its own lawsuit.

In its refusal letter, Harvard said the government’s demands violate the school’s First Amendment rights and other civil rights laws.

For the Trump administration, Harvard presents the first major hurdle in its attempt to force change at universities that Republicans say have become hotbeds of liberalism and antisemitism.