Comprehensive immigration legislation, President Bush’s top domestic priority this year, suffered a devastating blow in the Senate today that may prove to be the death knell for the bill in the 110th Congress.

On a 46-53 vote, the Senate failed to invoke cloture and limit debate on the bill (S 1639). It was the second time this month that backers of the legislation proved unable to muster the 60 votes needed to surmount opposition to the legislation from conservative Republicans and a mixed group of liberals and Democrats representing more generally GOP states. Indeed, the effort picked up only one new vote since June 7, when an effort to limit debate on an earlier version of the bill failed by 45-50.

The legislation before the Senate was the product of a “grand bargain” involving the White House and about a dozen senators from both parties. But the fragile compromise suited almost no one entirely.

It would allow millions of illegal immigrants to stay, receive legal status and ultimately earn citizenship; provide $4.4 billion in mandatory spending for border security and enforcement; and create a new temporary worker program.

The future now appears bleak for any immigration overhaul legislation in the remaining 18 months of the current Congress.

Refusal to invoke cloture now means “the bill is dead for this year,” Arlen Specter, R-Pa., warned before the vote. And with elections looming next year, it will not return before 2009, he predicted.

Majority Leader Harry Reid, D-Nev., did not go that far. “This is a legislative issue,” he said. “It will come back. It’s only a question of when.”