scholarly journals The role of negative selection in protein evolution revealed through the energetics of the native sate ensemble

2018 ◽  
Vol 86 (12) ◽  
pp. 1313-1313
Author(s):  
Jordan Hoffmann ◽  
James O. Wrabl ◽  
Vincent J. Hilser
Keyword(s):  
Protein Evolution ◽  
Negative Selection

scholarly journals A Role for Fas in Negative Selection of Thymocytes In Vivo

1998 ◽  
Vol 187 (9) ◽  
pp. 1427-1438 ◽  
Author(s):  
Hidehiro Kishimoto ◽  
Charles D. Surh ◽  
Jonathan Sprent
Keyword(s):  
Negative Selection ◽  
Cell Receptor ◽  
Staphylococcal Enterotoxin B ◽  
Thymic Medulla ◽  
Enterotoxin B ◽  
High Doses ◽  
Specific Peptide ◽  
Selection Of

To seek information on the role of Fas in negative selection, we examined subsets of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice injected with graded doses of antigen. In normal mice, injection of 1–100 μg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vβ8+ cells at the level of the semi-mature population of HSAhi CD4+ 8− cells found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection also caused marked elimination of Vβ8+ HSAhi CD4+ 8− thymocytes in lpr/lpr mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was induced by low-to-moderate doses of SEB (≤1 μg) but not by high doses (100 μg). Similar findings applied when T cell receptor transgenic mice were injected with specific peptide. These findings suggest that clonal elimination of semi-mature medullary T cells is Fas independent at low doses of antigen but Fas dependent at high doses. Previous reports documenting that negative selection is not obviously impaired in lpr/lpr mice could thus reflect that the antigens studied were expressed at only a low level.

scholarly journals Requirement for HLA-DR+ accessory cells in natural killing of cytomegalovirus-infected fibroblasts.

1986 ◽  
Vol 164 (1) ◽  
pp. 180-195 ◽  
Author(s):  
S Bandyopadhyay ◽  
B Perussia ◽  
G Trinchieri ◽  
D S Miller ◽  
S E Starr
Keyword(s):  
Negative Selection ◽  
Target Cells ◽  
Nk Activity ◽  
Ifn Alpha ◽  
Accessory Function ◽  
Hla Dr ◽  
Erythroleukemia Cells ◽  
Accessory Cells ◽  
Selection Experiments

The role of HLA-DR+ cells in NK activity against CMV-infected FS4 foreskin fibroblasts and K562 erythroleukemia cells was examined. When nonadherent PBMC were depleted of either HLA-DR+ or Leu-11b+ cells by treatment with mAbs plus C, NK activity against CMV-FS4 target cells was markedly reduced. In contrast, depletion of HLA-DR+ cells had no effect on NK activity against K562 target cells. When HLA-DR-depleted cells were added to Leu-11b-depleted cells, NK activity against CMV-FS4 was restored. Negative selection experiments indicated that the HLA-DR+ cells contributing to NK activity against CMV-FS4 are not B or T cells, while negative and positive selection experiments excluded a role for monocytes. Experiments in which HLA-DR- and Leu-11b- cells were mixed in varying proportions indicated that NK(CMV-FS4) is mediated by Leu-11b+ cells, while HLA-DR+ cells provide an accessory function. Irradiation (50 GY) abolished the NK effector function of Leu-11b+ cells, but not the accessory function of HLA-DR+ cells. The NK activity against CMV-FS4 of HLA-DR- cells was restored by the addition of rIFN-alpha or of cell-free supernatants generated by coculturing PBMC or Leu-11b- cells with CMV-FS4. The ability of these supernatants to restore NK activity of HLA-DR- cells was completely abrogated by the addition of neutralizing amounts of antibody to IFN-alpha. In related experiments, neutralization of IFN-alpha in NK assays had little or no effect on NK activity against CMV-FS4, suggesting that the accessory function of HLA-DR+ cells might be mediated by alternative mechanisms in addition to the secretion of extracellular IFN-alpha.

scholarly journals A Method for Positive and Negative Selection of Plasmodium falciparum Platelet-Mediated Clumping Parasites and Investigation of the Role of CD36

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e55453 ◽  
Author(s):  
Mònica Arman ◽  
Yvonne Adams ◽  
Gabriella Lindergard ◽  
J. Alexandra Rowe
Keyword(s):  
Plasmodium Falciparum ◽  
Negative Selection ◽  
Selection Of

scholarly journals Evolution of reproductive proteins from animals and plants

Reproduction ◽  
2006 ◽  
Vol 131 (1) ◽  
pp. 11-22 ◽  
Author(s):  
Nathaniel L Clark ◽  
Jan E Aagaard ◽  
Willie J Swanson
Keyword(s):  
Protein Evolution ◽  
Biological Process ◽  
Reproductive Proteins ◽  
Adaptive Diversification ◽  
Rapid Divergence ◽  
Fundamental Biological Process ◽  
Functional Consequences ◽  
Selective Forces ◽  
Reproductive Protein

Sexual reproduction is a fundamental biological process common among eukaryotes. Because of the significance of reproductive proteins to fitness, the diversity and rapid divergence of proteins acting at many stages of reproduction is surprising and suggests a role of adaptive diversification in reproductive protein evolution. Here we review the evolution of reproductive proteins acting at different stages of reproduction among animals and plants, emphasizing common patterns. Although we are just beginning to understand these patterns, by making comparisons among stages of reproduction for diverse organisms we can begin to understand the selective forces driving reproductive protein diversity and the functional consequences of reproductive protein evolution.

scholarly journals The Role of Dynamics in Protein Evolution

2011 ◽  
Vol 100 (3) ◽  
pp. 536a
Author(s):  
Tyler Glembo
Keyword(s):  
Protein Evolution

scholarly journals Role of the Multiple T Cell Receptor (TCR)-ζ Chain Signaling Motifs in Selection of the T Cell Repertoire

1997 ◽  
Vol 185 (5) ◽  
pp. 893-900 ◽  
Author(s):  
Elizabeth W. Shores ◽  
Tom Tran ◽  
Alexander Grinberg ◽  
Connie L. Sommers ◽  
Howard Shen ◽  
...  
Keyword(s):  
T Cell ◽  
Negative Selection ◽  
Selection Process ◽  
Cell Receptor ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Ligand Interaction ◽  
Competent Self ◽  
Selection Of

Immature thymocytes undergo a selection process within the thymus based on their T cell antigen receptor (TCR) specificity that results either in their maturation into functionally competent, self-MHC–restricted T cells (positive selection) or their deletion (negative selection). The outcome of thymocyte selection is thought to be controlled by signals transduced by the TCR that vary in relation to the avidity of the TCR–ligand interaction. The TCR is composed of four distinct signal transducing subunits (CD3-γ, -δ, -ε, and ζ) that contain either one (CD3-γ, -δ, -ε) or three (-ζ) signaling motifs (ITAMs) within their intracytoplasmic domains. A possible function for multiple TCR ITAMs could be to amplify signals generated by the TCR during selection. To determine the importance of the multiple TCR-ζ chain ITAMs in thymocyte selection, transgenes encoding α/βTCRs with known specificity were bred into mice in which ζ chains lacking one or more ITAMs had been genetically substituted for endogenous ζ. A direct relationship was observed between the number of ζ chain ITAMs within the TCR complex and the efficiency of both positive and negative selection. These results reveal a role for multiple TCR ITAMs in thymocyte selection and identify a function for TCR signal amplification in formation of the T cell repertoire.

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