CD6 and Linker of Activated T Cells are Potential Interaction Partners for T Cell-Specific Adaptor Protein.

The T cell-specific adaptor protein (TSAd) contains several protein interaction domains, and is merging as a modulator of T cell activation. Several interaction partners for the TSAd proline-rich region and phosphotyrosines have been identified, including the Src and Tec family kinases lymphocyte-specific protein tyrosine kinase and interleukin 2-inducible T cell kinase. Via its Src homology 2 (SH2) domain, TSAd may thus function as a link between these enzymes and other signalling molecules. However, few binding partners to the TSAd SH2 domain in T cells are hitherto known. Through the use of in silico ligand prediction, peptide spot arrays, pull-down and immunoprecipitation experiments, we here report novel interactions between the TSAd SH2 domain and CD6 phosphotyrosine (pTyr)629 and linker of activated T cells (LAT) pTyr171 , pTyr191 and pTyr226 .

Exploring the CLEC16A gene reveals a MS-associated variant with correlation to the relative expression of CLEC16A isoforms in thymus.

Genomewide association studies have implicated the CLEC16A gene in several autoimmune diseases, including multiple sclerosis (MS) and type 1 diabetes. However, the most associated single-nucleotide polymorphism (SNP) varies, and causal variants are still to be defined. In MS, two SNPs in partial linkage disequilibrium with each other, rs6498169 and rs12708716, have been validated at genomewide significance level. To explore the CLEC16A association in MS in more detail, we genotyped 57 SNPs in 807 Norwegian MS patients and 1027 Norwegian controls. Six highly associated SNPs emerged and were then replicated in two large independent sample sets (Norwegian and British), together including 1153 MS trios, 2308 MS patients and 4044 healthy controls. In combined analyses, SNP rs12708716 gave the strongest association signal in MS (P=5.3 x 10⁻8, odds ratio 1.18, 95% confidence interval=1.11-1.25), and was found to be superior to the other SNP associations in conditional logistic regression analyses. Expression analysis revealed that rs12708716 genotype was significantly associated with the relative expression levels of two different CLEC16A transcripts in thymus (P=0.004), but not in blood, possibly implying a thymus- or cell-specific splice regulation.

The spinothalamic system of the rat. I. Locations of cells of origin.

Horseradish peroxidase retrograde transport has been used to locate neurons of the rat spinal cord and lower medulla that project to the thalamus. Eight groups of spinothalamic cells are identified, some of which are anatomically continuous with thalamically projecting groups in the lower medulla. Most of the groups are seen only at the highest cervical levels, and several of them have not been previously recognised as spinothalamic relays. They are marginal layer (M), ventral border of the substantia gelatinosa (SGv), neck of the dorsal horn (N), lateral cervical nucleus (LCN), ventromedial portion of the dorsal horn (DHvm), intermediate gray zone (IGZ), dorsal portion of the ventral horn (VHd), and ventral portion of the ventral horn (VHv). Most of the cell bodies are contralateral to their thalamic terminations; only the VHd group is ipsilateral. The major finding conflicts with traditional concepts of the spinothalamic system, and concerns the rostrocaudal distribution of the cells of origin. With the sole exception of the DHvm group, the great majority of the thalamically projecting neurons of the rat are confined to the most rostral spinal levels (medulla/cord junction through C4). Below C4, most of the spinothalamic cells are concentrated in a single DHvm group between levels T9 and L4, probably concerned with hindlimb proprioception. The spinothalamic groups at high cervical levels may be relays for information ascending from lower regions. This might help to explain why, in man, surgical destruction of fibres crossing the midline in a single high cervical segment can cause a loss of pain sensation over most of the body.

The effects of capsaicin applied to peripheral nerves on responses of a group of lamina I cells in adult rats.

In adult rats, the sciatic and saphenous nerves on one side were treated topically with capsaicin. The capsaicin treatment had the effect of increasing the latency for withdrawal of the foot from hot water; 11-22 days later, the animals were decerebrated, and cells in the superficial dorsal horn of the lumbar cord with axons projecting in the contralateral dorsolateral funiculus (DLF) were examined electrophysiologically on the treated and untreated sides of the cord. HRP was applied to cut axons of the DLF at C4, in other rats, and retrograde labelling of cells in the lumbar cord indicated that most or all of the recordings in the capsaicin-treated animals were likely to originate from lamina 1. The dorsal horn cells, with receptive fields on the foot, showed decreased responses to electrically evoked afferent impulses in C fibres and grossly altered receptive fields. After capsaicin treatment, the proportion of cells responding to C afferents fell from 83% to 14%. The proportion responding only to C afferents and not to A afferents fell from 9% to 0%. The receptive fields (RFs) of these cells showed two gross abnormalities; 32% of the cells on the treated side had no apparent RF or an ill-defined, intermittent RF, whereas such cells were rare on the untreated side or in intact animals. By contrast 49% of the cells had grossly expanded RFs with an average area of 430 mm2 against the normal average size of 130 mm2.(ABSTRACT TRUNCATED AT 250 WORDS)