The affinity of the MHC/peptide/TCR interaction is thought to be one factor determining the differentiation of CD4+ T cells into Th1 or Th2 phenotypes. To study whether CD4+ cells generated under conditions favoring Th1 or Th2 responses select structurally different TCRs, Th1 and Th2 clones and lines were generated from nonobese diabetic and nonobese diabetic H2-E transgenic mice against the pe...

Although humanized antibodies have been highly successful in the clinic, all current humanization techniques have potential limitations, such as: reliance on rodent hosts, immunogenicity due to high non-germ-line amino acid content, v-domain destabilization, expression and formulation issues. This study presents a technology that generates stable, soluble, ultrahumanized antibodies via single-s...

The bias of αβ T cells for MHC ligands has been proposed to be intrinsic to the T-cell receptor (TCR). Equally, the CD4 and CD8 coreceptors contribute to ligand restriction by colocalizing Lck with the TCR when MHC ligands are engaged. To determine the importance of intrinsic ligand bias, the germ-line TCR complementarity determining regions were extensively diversified in vivo. We show that en...

Antibody discovery platforms have become an important source of both therapeutic biomolecules and research reagents. Massively parallel DNA sequencing can be used to assist antibody selection by comprehensively monitoring libraries during selection, thus greatly expanding the power of these systems. We have therefore constructed a rationally designed, fully defined single-chain variable fragmen...

Despite their favorable pharmacokinetic properties, single-chain Fv antibody fragments (scFvs) are not commonly used as therapeutics, mainly due to generally low stabilities and poor production yields. In this work, we describe the identification and optimization of a human scFv scaffold, termed FW1.4, which is suitable for humanization and stabilization of a broad variety of rabbit antibody va...

The relative contributions of germline gene variation and somatic mutation to immunoglobulin diversity were studied by comparing germline gene sequences with their rearranged counterparts for the mouse VH, V kappa, and V lambda genes. The mutation rate at the amino acid level was estimated to be 7.0% in the first and second complementarity-determining regions (CDRs) and 2.0% in the framework re...

BACKGROUND It has been documented that, independently from the specificity of the native antibody (Ab) for a given antigen (Ag), complementarity determining regions (CDR)-related peptides may display differential antimicrobial, antiviral and antitumor activities. METHODOLOGY/PRINCIPAL FINDINGS In this study we demonstrate that a synthetic peptide with sequence identical to V(H)CDR3 of a mouse...

Sheep is an important livestock in the world for meat, dairy and wool production. The third version of sheep reference genome has been recently assembled, but sheep DNA methylome has not been profiled yet. In this study, we report the comprehensive sheep methylome with 94.38% cytosine coverage at single base resolution by sequencing DNA samples from Longissimus dorsi of dizygotic Sunit sheep, w...

Disease mutations are traditionally thought to impair protein functionality by disrupting the folded globular structure of proteins. However, 22% of human disease mutations occur in natively unstructured segments of proteins known as intrinsically disordered regions (IDRs). This therefore implicates defective IDR functionality in various human diseases including cancer. The functionality of IDR...

AT THE END OF THIS MONTH, THE ANTARCTIC TREATY SUMMIT IN WASHINGTON, DC, WILL CELEBRATE the 50th anniversary of an international agreement that has been centered around science, promoting cooperation to manage nearly 10% of Earth for peaceful purposes since 1 December 1959 (see www.atsummit50.aq). As the world moves toward negotiating effective policies related to climate change, lessons from t...