Abstract
Immunosenescence is the gradual deterioration in immune system function associated with ageing. This decline is partly due to involution of the thymus, which leads to a reduction in the output of naive T cells into the circulating lymphocyte pool. Expansion of existing naive and memory T cell populations, to compensate for the reduction in thymic output, can lead to reduced diversity in the T cell repertoire with increasing age, resulting in impairment of immune responses to novel antigenic challenges, such as during infection and vaccination. Since associations between T cell repertoire and age have only been examined in a limited number of species, to gain further insights into this relationship, we have investigated age-related changes in the canine T cell receptor (TCR) repertoire.Blood samples were obtained from Labrador retriever dogs of varying ages and variation in the complementary determining region 3 (CDR3) of the T cell receptor beta (TCRB) chain was investigated. CDR3 size spectratyping was employed to evaluate clonal expansion/deletion in the T cell repertoire, allowing identification of profiles within individual variable (V) region families that skewed away from a Gaussian distribution. Older dogs (10–13 years) were found to have an increased number of TCRB V gene spectratypes that demonstrated a skewed distribution, compared with young dogs (≤3 years). Additionally, there was a reduction in the number of clonal peaks present in the spectratypes of old dogs, compared with those of young dogs. The study findings suggest that there is an age-associated disturbance in the diversity of the T cell receptor repertoire in dogs.
Highlights
In 2012, we highlighted TMEM165 as the first member of the Uncharacterized Protein Family 0016 (UPF0016) related to human diseases
Since Gdt1p and Pmr1p are two Golgi proteins involved in the regulation of the Golgi Ca2 +/Mn2 + homeostasis, glycosylation defect in gdt1Δ/pmr1Δ double knock-out strains was analyzed in the absence and the presence of increasing Ca2 + concentrations (Fig. 1)
Our results demonstrate that (i) the Golgi glycosylation defect observed in pmr1p deficient cells results from a lack of Golgi intraluminal Mn2 +, (ii) that the rescue of the glycosylation defect in pmr1Δ strains by the intraluminal Golgi Ca2 + requires the activity of Gdt1p
Summary
In 2012, we highlighted TMEM165 as the first member of the Uncharacterized Protein Family 0016 (UPF0016) related to human diseases. Defects in TMEM165 lead to a rare inherited disorder named CDG for Congenital Disorders of Glycosylation in which Golgi glycosylation process is affected. Archaea, yeast, plants and animals, members of the UPF0016 family share two highly conserved regions as signature motifs: E-x-G-D-[KR] [1]. Many evidences show that these two motifs form the pore of the protein and regulate the functionality of the UPF0016 members. The precise cellular functions of these proteins remain to be fully characterized and are under debate. It was previously reported that Gdt1p was involved in Ca2 + transport playing an important role in Ca2 +
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