RESUMO
We have used a novel T cell selection strategy to isolate a mutant of an H-2d/f murine macrophage line defective in its ability to present antigen to some Ed-restricted helper T cells. This mutant has an amino acid substitution in the alpha 2 domain of the Ed molecule. The mutation changes the sequence at codon 177 from ACC to CAC, which results in a threonine to histidine substitution and appears to be the first in vitro mutation to have arisen by genetic recombination. Even though the mutation is distal to the proposed antigen-binding groove, it affects antigen presentation, presumably by altering the scaffolding for the antigen-binding groove. This type of mutant might not be readily isolated using other selection techniques.
Assuntos
Antígenos de Histocompatibilidade Classe II/imunologia , Ativação Linfocitária , Linfócitos T Auxiliares-Indutores/imunologia , Sequência de Aminoácidos , Animais , Células Apresentadoras de Antígenos/imunologia , Sequência de Bases , Linhagem Celular , DNA/genética , Antígenos de Histocompatibilidade Classe II/genética , Camundongos , Dados de Sequência Molecular , Recombinação GenéticaRESUMO
The sulfated octapeptide of cholecystokinin (CCK-8) was infused intraperitoneally into 7 free-feeding male Sprague Dawley rats over a 6-day period. Infusions were given near the end of each free-feeding meal (1.87 microgram/meal/rat), and also during the intermeal interval in gradually increasing doses (0.10-0.63 microgram/5 min/rat). Food intake was continuously monitored and the infusions were controlled by microcomputer. Meal patterns, total food intake, and body weights during drug infusion were compared with data collected during a baseline period when only saline was infused. Meal-contingent CCK-8 infusion produced a significant 29.9% decrease in meal size which persisted throughout the drug-infusion period. Intermeal infusion of CCK-8 failed to prolong the intermeal interval (IMI) but it did initially prevent the compensatory decrease in IMI and increased feeding frequency expected after meal size was reduced. By the last day of drug infusion, total daily food intake recovered to baseline levels due to increased feeding frequency. Body weight was only transiently reduced by CCK-8 infusion. These findings show that tolerance does not develop to the action of CCK-8 to suppress meal size, and the administration of exogenous CCK-8 to free-feeding rats does not persistently prolong the intermeal interval.
