Chemokines are important mediators of the immune response that are responsible for the trafficking of immune cells between lymphoid organs and migration towards sites of inflammation.Using phage display selection and a functional screening approach, we have isolated a panel of single-chain fragment variable (scFv) capable of neutralizing the activity of the human chemokine CXCL10 (hCXCL10). One...

Immunoglobulin sequences from an individual Xenopus laevis froglet were analyzed for combinatorial and junctional diversity. In an animal with about 10(6) B lymphocytes, at least 26 out of the 56 VH1 genes available in a diploid genome were expressed, as were all JH segments. Junctional diversity was similar to that observed in Xenopus tadpole sequences, that is, little or no N diversification ...

The crystal structure of a mutant T cell receptor (TCR) V alpha domain containing a grafted third complementarity-determining region (CDR3) from a different V alpha was determined at 2.3 A resolution by molecular replacement using the wild-type V alpha structure as a search model. Like the wild-type V alpha domain, the mutant crystallized as a homodimer very similar to TCR V alpha V beta and an...

Binding of the T cell receptor (TCR) to a bacterial superantigen (SAG) results in stimulation of a large population of T cells and subsequent inflammatory reactions. To define the functional contribution of TCR residues to SAG recognition, binding by 24 single-site alanine substitutions in the TCR Vbeta domain to Staphylococcus aureus enterotoxin (SE) C3 was measured, producing an energy map of...

In this work, to study the emergence of the H chain V region repertoire during mammalian evolution, we present an analysis of 25 independent H chain V regions from a monotreme, the Australian duck-billed platypus, Ornithorhynchus anatinus. All the sequences analyzed were found to form a single branch within the clan III of mammalian V region sequences in a distance tree. However, compared with ...

We have hypothesized that in the prenegative selection TCR repertoire, many somatically generated complementary-determining region (CDR) 3 loops combine with evolutionarily selected germline Valpha/Vbeta CDR1/CDR2 loops to create highly MHC/peptide cross-reactive T cells that are subsequently deleted by negative selection. Here, we present a mutational analysis of the Vbeta CDR3 of such a cross...

Calculation of the electrostatic potential of protein-protein complexes has led to the general assertion that protein-protein interfaces display "charge complementarity" and "electrostatic complementarity". In this study, quantitative measures for these two terms are developed and used to investigate protein-protein interfaces in a rigorous manner. Charge complementarity (CC) was defined using ...

Plant diversity generally promotes biomass production, but how the shape of the response curve changes with time remains unclear. This is a critical knowledge gap because the shape of this relationship indicates the extent to which loss of the first few species will influence biomass production. Using two long-term (≥13 years) biodiversity experiments, we show that the effects of diversity on b...

Receptor editing is a mechanism of self-tolerance used in newly generated B cells. The expressed heavy (H) or light (L) chain of an autoreactive receptor is replaced by upstream V genes which eliminate or modify autoreactivity. Editing of anti-DNA receptors has been characterized in anti-DNA transgenic mouse models including 3H9, 3H9/56R, and their revertant 3H9GL. Certain L chains, termed edit...

The crystal structure of the complex between hen egg lysozyme and the Fv fragment of a humanized antilysozyme antibody was determined to 2.7-A resolution. The structure of the antigen combining site in the complex is nearly identical to that of the complexed form of the parent mouse antibody, D1.3. In contrast, the combining sites of the unliganded mouse and humanized antilysozymes show moderat...