Successive crystal structure snapshots suggest the basis for MHC class i peptide loading and editing by tapasin

MHC-I epitope presentation to CD8 + T cells is directly dependent on peptide loading and selection during antigen processing. However, the exact molecular bases underlying peptide selection and binding by MHC-I remain largely unknown. Within the peptideloading complex, the peptide editor tapasin is key to the selection of MHC-I-bound peptides. Here, we have determined an ensemble of crystal structures of MHC-I in complex with the peptide exchange-associated dipeptide GL, as well as the tapasin-associated scoop loop, alone or in combination with candidate epitopes. These results combined with mutation analyses allow us to propose a molecular model underlying MHC-I peptide selection by tapasin. The N termini of bound peptides most probably bind first in the N-terminal and middle region of the MHC-I peptide binding cleft, upon which the peptide C termini are tested for their capacity to dislodge the tapasin scoop loop from the F pocket of the MHC-I cleft. Our results also indicate important differences in peptide selection between different MHC-I alleles

Effect of grazing sorghum (Sorghum bicolor) infected with ergot (Claviceps africana) on beef cattle

14 heifers aged 3 to 4 years (Bos indicus × Bos taurus), including 9 in the second month of pregnancy, plus 9 steers aged about 14 months (Bos taurus) were grazed on sorghum infected with C. africana ergot for 28 days. Estimated average daily dry matter intake over the trial period was 9.0 kg. Daily alkaloid intakes (mostly dihydroergosine) were estimated to be about 35 mg/head. Over the course of the trial, there was a slight decline in body weight of the heifers, which averaged 405 kg initially and 400 kg after 28 days. The weight of the steers averaged 283 initially and 295 kg after 28 days (an apparent gain of 0.4 kg/day). Plasma prolactin concentrations (whole herd) of 140 mg/litre were reduced to 79 mg/litre after 14 days of grazing and were 93 mg/litre after 28 days. These changes in steers (decrease after 14 days and increase from 14 to 28 days) were both significant. There also were reductions in mean prolactin concentrations in both pregnant and non-pregnant heifers after 14 days grazing, but these were not significant. The steers had lower prolactin concentrations than the heifers and showed a greater response to grazing. No clinical abnormalities were detected in any of the cattle