记忆T细胞平行分化模型的理论研究

为了从理论上讨论T细胞记忆维持机制的问题,基于T细胞的平行分化假说建立了非线性理论模型,利用此模型,在不同的抗原初值下得到了三种不同类型的应答。用优化剂量的抗原免疫生物体并且抗原存在时记忆能持续很长的时间,而失去抗原的同时将失去记忆,得出记忆T细胞平行分化模型确有记忆机制;并发现记忆强度与剩余抗原量有直接的关系,还进一步讨论了记忆细胞寿命的问题,并对体外情况作了预言。     

Biophysical studies of a transmembrane peptide derived from the T cell antigen receptor

Summary Core peptide (CP) is a unique peptide derived from the transmembrane sequence of T cell antigen receptor (TCR)-alpha chain and is capable of inhibiting the immune response both invitro and in animal models of T cell mediated inflammation. The structure of CP, with sequence GLRILLLKV, is similar to the amphipathic region of many peptides. Unlike antimicrobial peptides, however, which damage cell membranes, electron microscopy and propidium iodide exclusion assays on cell membranes suggest that CP does not create pores and may act by interfering with signal transduction at the membrane level. To investigate this effect further we report the results of³¹P and²H solid-state NMR spectroscopy of CP on model membranes. As predicted, even at high concentrations of CP, the structure of model membranes was not significantly perturbed. Only at the very high peptide-to-lipid molar ratio of 1∶10 significant effects on the model membranes were observed. We conclude that CP does not destroy the integrity of the lipid bilayer.     

The arbitrium system controls prophage induction

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GABAB Receptor Constituents Revealed by Tandem Affinity Purification from Transgenic Mice

GABA_B receptors function as heterodimeric G-protein-coupled receptors for the neurotransmitter γ-aminobutyric acid (GABA). Receptor subtypes, based on isoforms of the ligand-binding subunit GABA_B1, are thought to involve a differential set of associated proteins. Here, we describe two mouse lines that allow a straightforward biochemical isolation of GABA_B receptors. The transgenic mice express GABA_B1 isoforms that contain sequences for a two-step affinity purification, in addition to their endogenous subunit repertoire. Comparative analyses of purified samples from the transgenic mice and wild-type control animals revealed two novel components of the GABA_B1 complex. One of the identified proteins, potassium channel tetramerization domain-containing protein 12, associates with heterodimeric GABA_B receptors via the GABA_B2 subunit. In transfected hippocampal neurons, potassium channel tetramerization domain-containing protein 12 augmented axonal surface targeting of GABA_B2. The mice equipped with tags on GABA_B1 facilitate validation and identification of native binding partners of GABA_B receptors, providing insight into the molecular mechanisms of synaptic modulation.     

Lymphocyte recognition of H-2 antigen in liposomes

Liposomes containing purified H-2K^k will specifically stimulate generation of a secondary allogeneic cytolytic T lymphocyte response. Effective recognition was found to depend on the structure of the liposomes. Including detergent-insoluble plasma membrane matrix during formation resulted in liposomes having two- to fourfold more activity than those prepared using just lipid and H-2.     

A Conservative Point Mutation in a Dynamic Antigen-binding Loop of Human Immunoglobulin λ6 Light Chain Promotes Pathologic Amyloid Formation

Immunoglobulin light chain (LC) amyloidosis (AL) is a life-threatening human disease wherein free mono-clonal LCs deposit in vital organs. To determine what makes some LCs amyloidogenic, we explored patient-based amyloidogenic and non-amyloidogenic recombinant LCs from the λ6 subtype prevalent in AL. Hydrogen-deuterium exchange mass spectrometry, structural stability, proteolysis, and amyloid growth studies revealed that the antigen-binding CDR1 loop is the least protected part in the variable domain of λ6 LC, particularly in the AL variant. N32T substitution in CRD1 is identified as a driver of amyloid formation. Substitution N32T increased the amyloidogenic propensity of CDR1 loop, decreased its protection in the native structure, and accelerated amyloid growth in the context of other AL substitutions. The destabilizing effects of N32T propagated across the molecule increasing its dynamics in regions ∼30 Å away from the substitution site. Such striking long-range effects of a conservative point substitution in a dynamic surface loop may be relevant to Ig function. Comparison of patient-derived and engineered proteins showed that N32T interactions with other substitution sites must contribute to amyloidosis. The results suggest that CDR1 is critical in amyloid formation by other λ6 LCs.     

Interaction between the light quality and flowering time pathways in Arabidopsis

Flowering in Arabidopsis is accelerated by a reduced ratio of red light to far-red light (R/FR), which indicates the proximity of competitive vegetation. By exploiting the natural genetic variation in flowering time responses to low R/FR, we obtained further insight into the complex pathways that fine-tune the transition to flowering in Arabidopsis. The Bla-6 ecotype does not flower significantly earlier in response to low R/FR, but is still able to display other features of shade avoidance, suggesting branching of low R/FR signalling. Here we show that the muted flowering response of Bla-6 is due to high levels of the floral repressor FLOWERING LOCUS C (FLC), conferred by a combination of functional FLC and FRIGIDA ( FRI ) alleles with a 'weak' FY allele. The Bla-6 FY allele encodes a protein with a corrupted WW binding domain, and we provide evidence that this locus plays a key role in the natural variation in light quality-induced flowering in Arabidopsis. In Bla-6, FLC blocks promotion to flowering by reduced R/FR by inhibiting expression of the floral integrator FLOWERING LOCUS T ( FT ) in a dose-dependent manner. Reduction of FLC removes this obstruction, and Bla6 plants then exhibit strong induction of FT and flower early in response to a low R/FR signal. This paper illustrates the intricate interaction of environmental signals and genetic factors to regulate flowering in Arabidopsis.     

Primary structure of the tail sheath protein of bacteriophage T4 and its gene

Complete sequence determination of gene 18 encoding the tail sheath protein was carried out mainly by the Maxam-Gilbert method. Approximately 40 peptides contained in a tryptic digest and a lysyl endopeptidase digest of gp 18 were isolated by reversed-phase high-performance liquid chromatography. All the peptides were identified along the nucleotide sequence of gene 18 based on the amino acid compositions. These peptides cover 88% of the total primary structure. Furthermore, the amino acid sequences of 9 of the 40 peptides were determined by a gas-phase protein sequencer; one of them turned to be the N-terminal one. The C-terminal peptide in the tryptic digest was isolated from the unadsorbed fraction of affinity chromatography on immobilized anhydrotrypsin and the amino acid sequence was also determined. Thus, the complete primary structure of gp 18 was determined; it has 658 amino acid residues and a molecular weight of 71,160.This article was presented during the proceedings of the International Conference on Macromolecular Structure and Function, held at the National Defence Medical College, Tokorozawa, Japan, December 1985.     

Mitochondrial Oxidative Phosphorylation Regulates the Fate Decision between Pathogenic Th17 and Regulatory T Cells

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