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T cells recognize a complex of peptide Ag bound within the groove of MHC-encoded molecules. Although many studies have attempted to correlate TCR gene expression with specificity for particular Ag/MHC combinations, it is still not clear exactly how the TCR physically interacts with its cognate ligand. We have analyzed transgenic mice that carry a rearranged gene encoding a V beta 5.2+ TCR beta-chain derived from the CD8+ CTL clone B3, which is specific for chicken OVA+H-2Kb. Surprisingly, we have found that peripheral lymphocytes isolated from naïve V beta 5.2 transgenic mice can generate a strong primary anti-OVA CTL response when stimulated in vitro with OVA+H-2b, whereas generation of even a weak anti-OVA response from nontransgenic littermates requires in vivo priming. This response is Ag specific, because the transgenic mice are unable to respond with or without priming to vesicular stomatitis virus, which contains a dominant epitope presented in the context of H-2Kb. The precursor frequency of OVA-specific CTL in unprimed V beta 5.2 transgenic mice is approximately 30-fold higher than that in nontransgenic littermate controls. Reverse transcription-PCR analyses demonstrate that OVA-specific CTL lines derived from unprimed V beta 5.2 transgenic mice express a variety of TCR V alpha elements, indicating that the transgenic anti-OVA response is not solely due to the reconstitution of the original B3 TCR. In fact, our data suggest that even a nontransgenic V beta 5+ TCR is intrinsically OVA specific. First, five separate OVA-specific oligoclonal CTL lines derived from individual nontransgenic mice demonstrate dramatic skewing toward expression of V beta 5.1+ or V beta 5.2+ TCR over the course of several in vitro stimulations. Second, sorting for V beta 5+CD8+ nontransgenic cells enriches for OVA-specific CTL. However, peptide antagonism experiments using mutant forms of the Kb-restricted OVA peptide reveal distinct differences between the recognition patterns of two individual OVA-specific CTL lines derived from unprimed V beta 5.2 transgenic mice. These experiments support the notion that a discrete portion of the responding TCR can heavily influence but not necessarily be solely sufficient for the recognition of a peptide Ag presented in the cleft of an MHC-encoded molecule.
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Interim coach Steve Wilks told reporters Monday morning that P.J. Walker is dealing with a high ankle sprain suffered in Thursday night's win over the Atlanta Falcons, thrusting Mayfield back into the starting lineup.
Wilks noted that Walker played through the injury but wouldn't be available against Baltimore. The coach did not indicate Walker's timeline to return but doesn't anticipate the QB going on injured reserve at this point.
Mayfield started the first five games of the season but struggled mightily, completing 54.9 percent of his passes for 962 yards with four touchdowns and four interceptions. He suffered an ankle injury of his own in Week 5 that opened the door for Walker to take over the starting role.
Mayfield replaced Walker at halftime of Week 9's blowout loss to Cincinnati and played well, but at the time, Wilks decided to stick with Walker, who has led the Panthers to two of their three victories on the season.
The news means Mayfield will face a familiar foe in Baltimore. The QB started eight games against the Ravens during his four seasons in Cleveland. The Browns went 3-5 in those starts, with Mayfield generating an 83.2 passer rating with 13 TDs to 9 INTs versus Baltimore.
NFL Commissioner Roger Goodell addressed a number of key league issues -- including diversity efforts, officiating and player health and safety -- during his news conference on Wednesday ahead of Super Bowl LVII.
San Francisco 49ers quarterback Brock Purdy will meet with Dr. Keith Meister in Dallas on Feb. 21 and plans to have surgery to repair his torn UCL on the 22nd, NFL Network Insider Ian Rapoport reported, per sources informed of the decision.
With the Commanders likely looking for a new starter for the 2023 season, head coach Ron Rivera said Wednesday that second-year quarterback Sam Howell will get the first crack at proving he's worthy of the position.
Talking on Super Bowl Live on Wednesday, running back Christian McCaffrey was the latest player to discuss the 49ers' feelings of disappointment surrounding their NFC Championship Game loss to the Eagles, saying it means the team will "have a lot of fuel this offseason."
Rob Gronkowski once again emphasized that his second retirement was for good on Tuesday, saying he's looking forward to the possibility of connecting with Tom Brady as FOX broadcasters now that the QB has joined him in retirement.
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The No. 5 Arizona Wildcats (13-1) look like the class of the Pac-12 once again, but the Washington Huskies (9-6) will take their shot at handing them their second conference loss of the season on Thursday. The Huskies may have to do it short-handed, however, as senior guard PJ Fuller II could miss his second consecutive game with an undisclosed injury. He scored 11 points with three rebounds and two steals at Arizona in the first game between the programs last year.
Tip-off from McKale Memorial Center is set for 11 p.m. ET, where Arizona is 8-0 this season. The Wildcats are favored by 18.5 points in the latest Arizona vs. Washington odds from Caesars Sportsbook, and the over/under is set at 154.5. Before entering any Washington vs. Arizona picks, you'll want to see the college basketball predictions from the model at SportsLine.
The SportsLine Projection Model simulates every Division I college basketball game 10,000 times. The model enters Week 9 of the season 30-16 on all-top rated college basketball picks, returning more than $800 for $100 players. Anybody who has followed it has seen huge returns.
Arizona pulled out a solid win over Arizona State on Saturday, 69-60. Forward Azuolas Tubelis finished with a game-high 21 points to go with nine rebounds. Center Oumar Ballo had 12 points and 12 boards while Kerr Kriisa also had 12 points with five assists in the win.
As expected of a top-five program, Arizona ranks second in the nation in team shooting percentage (52.2%). Ballo has been the most efficient scorer, and all of his work around the basket has helped him make 71.9% of his shots this season. The Wildcats are also second in the country in assists, and Kriisa leads the team with six dimes per contest.
Washington will need a big turnaround to win on Thursday against Arizona after it was thoroughly defeated by UCLA on Sunday, 74-49. Braxton Meah was the lone bright spot in the game for the Huskies, after he made 9-of-10 shots to score a game-high 20 points. Noah Williams had the kind of night that summed up the performance of the rest of the team when he made just 2-of-9 attempts for five points in 36 minutes played.
Even though Washington has lost its last three games, the Huskies have done some things well this season, particularly defending the rim. Washington averages 6.1 blocks per game, which is fourth-best in the nation. Unfortunately, their top post defender, Franck Kepnang (1.9 bpg) is done for the year with a knee injury. Meah has also been a formidable defender, with 1.6 blocks per start.
The model has simulated Arizona vs. Washington 10,000 times and the results are in. The model is leaning Under, and it's also generated a point-spread pick that is hitting in over 50% of simulations. You can only see the pick at SportsLine.
Who wins Arizona vs. Washington? And which side of the spread hits more than 50% of the time? Visit SportsLine right now to see which side of the spread you need to jump on, all from the computer model that has crushed its college basketball picks, and find out!
The No. 1-seeded Heat, who lead the first-round playoff series 3-1, will now try to close out the Hawks while down at least two starters. Point guard Kyle Lowry will miss his second straight game with a hamstring injury while forward P.J. Tucker is questionable with a calf strain.
Butler has not only been the Heat's best player in the series, but also one of the best players in the entire NBA playoffs thus far. Through four games, the 32-year-old is averaging 30.5 points, 7.8 rebounds, 5.8 assists and 2.8 steals while shooting 54.3% from the field and 43.8% from 3-point range. Butler shot just 23.3% from deep during the regular season.
Career Record: 10 Years, 74-49, .602 Win% (at major schools)Bowl Record: 7 Games, 5-2, .714 Win% (at major schools)As Player: 1999-2003(Full Stats)
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