An Ig Transmembrane Domain Motif Improves the Function of TCRs Transduced in Human T Cells: Implications for Immunotherapy.

Adoptive transfer of T lymphocytes (ACT) engineered with T-cell receptors (TCRs) of known antitumor specificity is an effective therapeutic strategy. However, a major constraint of ACT is the unpredictable interference of the endogenous TCR α and β chains in pairing of the transduced TCR. This effect reduces the efficacy of the genetically modified primary T cells and carries the risk of generating novel TCR reactivities with unintended functional consequences.

Evolution of the complement system C3 gene in Antarctic teleosts.

Notothenioidei are typical Antarctic teleosts evolved to adapt to the very low temperatures of the Antarctic seas. Aim of the present paper is to investigate sequence and structure of C3, the third component of the complement system of the notothenioid Trematomus bernacchii and Chionodraco hamatus. We determined the complete nucleotide sequence of two C3 isoforms of T.

The structure of the CD3 ζζ transmembrane dimer in POPC and raft-like lipid bilayer: a molecular dynamics study.

Plasma membrane lipids significantly affect assembly and activity of many signaling networks. The present work is aimed at analyzing, by molecular dynamics simulations, the structure and dynamics of the CD3 ζζ dimer in palmitoyl-oleoyl-phosphatidylcholine bilayer (POPC) and in POPC/cholesterol/sphingomyelin bilayer, which resembles the raft membrane microdomain supposed to be the site of the signal transducing machinery. Both POPC and raft-like environment produce significant alterations in structure and flexibility of the CD3 ζζ with respect to nuclear magnetic resonance (NMR) model: the dimer is more compact, its secondary structure is slightly less ordered, the arrangement of the Asp6 pair, which is important for binding to the Arg residue in the alpha chain of the T cell receptor (TCR), is stabilized by water molecules.

Evolutionary analysis of Antarctic teleost Toll-like receptor 2.

In the present study we address the investigation of TLR2 evolutionary selection in two Antarctic teleosts, Trematomus bernacchii (Nototheniidae) and Chionodraco hamatus (Channichthyidae). The nucleotide sequence of TLR2 has been determined in both species, encoding 20 leucine-rich repeats (LRRs) in the extracellular region and a classical Toll/IL-1R (TIR) domain in the intracellular region. High expression level of T.

Antarctic teleost immunoglobulins: more extreme, more interesting.

We have investigated the immunoglobulin molecule and the genes encoding it in teleosts living in the Antarctic seas at the constant temperature of -1.86 °C. The majority of Antarctic teleosts belong to the suborder Notothenioidei (Perciformes), which includes only a few non-Antarctic species.

An evolutionary conserved motif is responsible for immunoglobulin heavy chain packing in the B cell membrane.

All species of vertebrates synthesize immunoglobulin molecules, which differ in an number of aspects but also share a few common features responsible for their function, such as the presence of a transmembrane domain in the membrane bound form of the immunoglobulin heavy chain (IgTMD) that ensures communication with the signal transducing Igα-Igβ peptides. We have analyzed the gene sequence encoding the IgTMD of different heavy chain isotypes of very distant species, from shark to mammals. The IgTMD sequences show a high degree of sequence identity and their encoding nucleotide sequences were shown to be subject to purifying selection at most sites.

Evolution of the Antarctic teleost immunoglobulin heavy chain gene.

Notothenioid teleosts underwent major modifications of their genome to adapt to the cooling of the Antarctic environment. In order to identify specific features of the Antarctic teleost immunoglobulin, transcripts encoding the constant region of the IgM heavy chain from 13 Antarctic and non-Antarctic notothenioid species were sequenced. The primary mRNA splicing for the membrane form was found to be atypical in the majority of Antarctic species, because it led to exclusion of two entire constant exons, and to inclusion of 39-nucleotide exons encoding an unusually long Extracellular Membrane-Proximal Domain (EMPD).

Structure and dimerization of the teleost transmembrane immunoglobulin region.

The immune system cells express activating receptors, which consist of a dimeric ligand-binding molecule associated with a signal transducing dimer. The communication between the receptor partners depends primarily on the interactions between their membrane-embedded segments. In the B cell receptor (BCR) the sequence traversing the lipid bilayer of the immunoglobulin (IgTM) is highly conserved among species.

Immunoglobulin light chain isotypes in the teleost Trematomus bernacchii.

Three immunoglobulin light chain (IgL) isotypes TrbeL1, TrbeL2, and TrbeL3 were identified in the Antarctic teleost Trematomus bernacchii by immunoscreening a cDNA expression library, and using RT-PCR, and 5' RACE. One of them was distinguished in two subisotypes TrbeL1A and TrbeL1B. Real-time PCR experiments showed that the different isotypes were expressed in similar ratios in the various tissues analyzed.