Biomedical subjects

T P Quinn

Publications and source records attributed to T P Quinn.

At least 19 recordsLinked to original sources

PubMed2007

Material model measurements and predictions for a random pore poly(epsilon-caprolactone) scaffold.

We investigated material models for a polymeric scaffold used for bone. The material was made by co-extruding poly(epsilon-caprolactone) (PCL), a biodegradable polyester, and poly(ethylene oxide) (PEO). The water soluble PEO was removed resulting in a porous scaffold. The stress-strain curve in compression was fit with a phenomenological model in hyperbolic form. This material model will be useful for designers for quasi-static analysis as it provides a simple form that can easily be used in finite element models. The ASTM D-1621 standard recommends using a secant modulus based on 10% strain. The resulting modulus has a smaller scatter in its value compared with the coefficients of the hyperbolic model, and it is therefore easier to compare differences in material processing and ensure quality of the scaffold. A prediction of the small-strain elastic modulus was constructed from images of the microstructure. Each pixel of the micrographs was represented with a brick finite element and assigned the Young's modulus of bulk PCL or a value of 0 for a pore. A compressive strain was imposed on the model and the resulting stresses were calculated. The elastic constants of the scaffold were then computed with Hooke's law for a linear-elastic isotropic material. The model was able to predict the small-strain elastic modulus measured in the experiments to within one standard deviation. Thus, by knowing the microstructure of the scaffold, its bulk properties can be predicted from the material properties of the constituents.

Bone Substitutes↗

PubMed2006

Comparison of mechanical behavior among the extrapulmonary arteries from rats.

Results of comparative tests on pulmonary arteries from untreated Long-Evans rats are presented from three sections of the artery: the trunk, and the right and left main extrapulmonary arteries. Analyses were conducted looking for mechanical differences between the flow (longitudinal) and circumferential directions, between the right and left main arteries, and between each of the mains and the trunk. The mechanical properties of rat pulmonary arteries were obtained with a bubble inflation technique. A flat disk of rat pulmonary artery was constrained at the periphery and inflated, and the geometry of the resulting bubble of material recorded from six different angles. To analyze the data, the area under the stress-strain curve was calculated for each test and orientation. This area, related to the strain-energy density, was calculated at stress equal to 200kPa, for the purpose of statistical comparison. The mean values for the area show that the trunk is less compliant than the main arteries; this difference is supported by histological evidence. When comparing the circumferential and longitudinal properties of the arteries, differences are found for the trunk and left main arteries, but with opposite orientations being more compliant. The mean values for the two orientations for the right main artery are statistically identical. There was indication of significant difference in mechanical properties between the trunk and the main arteries. The left main artery in the circumferential orientation is highly compliant and appears to strongly influence the likelihood that significant differences will exist when included in a statistical population. These data show that each section of the extrapulmonary arterial system should not be expected to behave identically, and they provide the baseline mechanical behavior of the pulmonary artery from normotensive rats.

Animals↗

PubMed2006

An empirical verification of population assignment methods by marking and parentage data: hatchery and wild steelhead (Oncorhynchus mykiss) in Forks Creek, Washington, USA.

Assignment tests are increasingly applied in ecology and conservation, although empirical comparisons of methods are still rare or are restricted to few of the available approaches. Furthermore, the performance of assignment tests in cases with low population differentiation, violations of Hardy-Weinberg equilibrium and unbalanced sampling designs has not been verified. The release of adult hatchery steelhead to spawn in Forks Creek in 1996 and 1997 provided an opportunity to compare the power of different assignment methods to distinguish their offspring from those of sympatric wild steelhead. We compared standard assignment methods requiring baseline samples (frequency, distance and Bayesian) and clustering approaches with and without baseline information, using six freely available computer programs. Assignments were verified by parentage data obtained for a subset of returning offspring. All methods provided similar assignment success, despite low differentiation between wild and hatchery fish (F(ST) = 0.02). Bayesian approaches with baseline data performed best, whereas the results of clustering methods were variable and depended on the samples included in the analysis and the availability of baseline information. Removal of a locus with null alleles and equalizing sample sizes had little effect on assignments. Our results demonstrate the robustness of most assignment tests to low differentiation and violations of assumptions, as well as their utility for ecological studies that require correct classification of different groups.

Alleles↗

PubMed2004

Constitutive models for a poly(e-caprolactone) scaffold.

We investigate material models for a porous, polymeric scaffold used for bone. The material was made by co-extruding poly(e-caprolactone) (PCL), a biodegradable polyester, and poly(ethylene oxide) (PEO). The water soluble PEO was removed resulting in a porous scaffold. The stress-strain curve in compression was fit with a phenomenological model in hyperbolic form. This material model will be useful for designers for quasi-static analysis as it provides a simple form that can easily be used in finite element models. The ASTM D-1621 standard recommends using a secant modulus based on 10% strain. The resulting modulus has a smaller scatter in its value compared to the coefficients of the hyperbolic model, and it is therefore easier to compare material processing differences and ensure quality of the scaffold. A third material model was constructed from images of the microstructure. Each pixel of the micrographs was represented with a brick finite element and assigned the Young's modulus of bulk PCL or a value of 0 for a pore. A compressive strain was imposed on the model and the resulting stresses were calculated. The elastic constants of the scaffold were then computed using Hooke's law for a linear-elastic isotropic material. The model was able to predict the small strain Young's modulus measured in the experiments to within one standard deviation. Thus, by knowing the microstructure of the scaffold, its bulk properties can be predicted from the material properties of the constituents.

Bone Substitutes↗

PubMed2003

Migratory costs and contemporary evolution of reproductive allocation in male chinook salmon.

Energetically demanding migrations may impact the resources available for reproductive trait development and activity, and hence favour evolution of new investment strategies for remaining resources. We conducted a large-scale experiment to evaluate the proximate cost of migration on male reproductive investment in chinook salmon (Oncorhynchus tshawytscha) and contemporary evolution of reproductive allocation. Experimentally induced differences in migratory costs (17 km inland and 17 m elevation vs. 100 km and 430 m) influenced dorsal hump size and upper jaw length, two traits influencing male mating success that are developed during migration. Longer migration also reduced tissue energy reserves available for competition and length of breeding life. Corresponding shifts in the balance between natural and sexual selection appear to have been responsible for heritable population divergence in secondary sexual trait investment, in approximately 26 generations, following colonization of spawning sites with different migratory demands.

Adaptation, Physiological↗

PubMed2002

Reconstructing recent divergence: evaluating nonequilibrium population structure in New Zealand chinook salmon.

Newly established or perturbed populations are often the focus of conservation concerns but they pose special challenges for population genetics because drift-migration equilibrium is unlikely. To advance our understanding of the evolution of such populations, we investigated structure and gene flow among populations of chinook salmon that formed via natural straying following introduction to New Zealand in the early 1900s. We examined 11 microsatellite loci from samples collected in several sites and years to address two questions: (i) what population differentiation has arisen in the approximately 30 generations since salmon were introduced to New Zealand, relative to temporal variation within populations; and (ii) what are the approximate effective population sizes and amounts of gene flow in these populations? These questions are routinely addressed in studies of indigenous populations, but less often in the case of new populations and rarely with consideration of equilibrium assumptions. We show that despite the recent introduction, continued gene flow and high temporal variability among samples, detectable population structure has arisen among the New Zealand populations, consistent with their colonization pattern and isolation by geographical distance. Furthermore, we use simple individual-based simulations and estimates of effective population sizes to estimate the effective gene flow among drainages under likely nonequilibrium conditions. Similar methodology may be broadly applicable to other studies of population structure and phenotypic evolution under similar nonequilibrium, high gene flow conditions.

Animals↗

PubMed2001

A receptor for vascular endothelial growth factor that stimulates endothelial apoptosis.

Vascular endothelial growth factor (VEGF) is a dimeric angiogenic factor that is overexpressed by many tumors and stimulates tumor angiogenesis. VEGF initiates signaling by dimerizing the receptors VEGFR-1 and VEGFR-2. The Fas receptor stimulates apoptosis, and artificial dimerization of the Fas cytoplasmic domain has been shown to induce apoptosis. We constructed a chimeric receptor (VEGFR2Fas) combining the extracellular and transmembrane domains of VEGFR-2 with the cytoplasmic domain of Fas receptor. When VEGFR2Fas was stably expressed in endothelial cells in vitro, treatment with VEGF rapidly induced cell death with features characteristic of Fas-mediated apoptosis. These findings demonstrate that VEGFR2Fas functions as a VEGF-triggered death receptor and raise the possibility that introduction of VEGFR2Fas into tumor endothelium or tumor cells in vivo may convert tumor-derived VEGF from an angiogenic factor into an antiangiogenesis agent.

Animals↗

PubMed2001

The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium.

Interactions of metastatic cancer cells with vasculatory endothelium are critical during early stages of cancer metastasis. Understanding the molecular underpinnings of these interactions is essential for the development of new efficacious cancer therapies. Here we demonstrate that cancer-associated carbohydrate T antigen plays a leading role in docking breast and prostate cancer cells onto endothelium by specifically interacting with endothelium-expressed beta-galactoside-binding protein, galectin-3. Importantly, T antigen-bearing glycoproteins are also capable of mobilizing galectin-3 to the surface of endothelial cells, thus priming them for harboring metastatic cancer cells. The T antigen-mediated, tumor-endothelial cell interactions could be efficiently disrupted using synthetic compounds either mimicking or masking this carbohydrate structure. High efficiency of T antigen-mimicking and T antigen-masking inhibitors of tumor cell adhesion warrants their further development into antiadhesive cancer therapeutics.

Amino Acid Sequence↗

PubMed2001

Radiometallated receptor-avid peptide conjugates for specific in vivo targeting of cancer cells.

New receptor-avid radiotracers are being developed for site-specific in vivo targeting of a myriad of receptors expressed on cancer cells. This review exemplifies strategies being used to design radiometallated peptide conjugates that maximize uptake in tumors and optimize their in vivo pharmacokinetic properties. Efforts to produce synthetic peptide analogues that target the following three receptor systems are highlighted: Gastrin releasing peptide (GRP), alpha-melanocyte stimulating hormone (alpha-MSH), and guanylate cyclase-C (GC-C) receptors.

Animals↗

PubMed2001

Migratory costs and the evolution of egg size and number in introduced and indigenous salmon populations.

The trade-off between reproductive investment and migration should be an important factor shaping the evolution of life-history traits among populations following their radiation into habitats with different migratory costs and benefits. An experimentally induced difference in migratory rigor for families of chinook salmon (Oncorhynchus tshawytscha), of approximately 86 km and 413 m elevation, exacted a cost to somatic energy reserves (approximately 17% reduction in metabolizable mass) and ovarian investment (13.7% reduction in ovarian mass). This cost was associated with a reduction in egg size and paralleled the phenotypic pattern of divergence between two introduced New Zealand populations of common origin, presently breeding at sites with different migration distances. The genetic pattern of divergence of these same populations, detected under common rearing, was consistent with compensation for migratory costs (the population that migrates farther invested more in ovarian mass), but egg number more than egg size was associated with this evolution. These evolutionary patterns are consistent with what is known of the inheritance of these traits and with trade-offs and constraints favoring initial evolution in offspring number over offspring size. Analysis of egg number-size patterns of other Pacific salmon populations in their native range supported the hypothesis that migration strongly influences patterns of reproductive allocation, favoring a higher ratio of egg number to egg size with greater migration distance.

Animal Migration↗

PubMed2001

Evaluation of an (111)In-DOTA-rhenium cyclized alpha-MSH analog: a novel cyclic-peptide analog with improved tumor-targeting properties.

UNLABELLED: The aim of this study was to examine the effect of rhenium-mediated peptide cyclization on melanoma targeting, biodistribution, and clearance kinetics of the alpha-melanocyte-stimulating hormone (alpha-MSH) analog 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) coupled ReO-cyclized [Cys(3,4,10),D-Phe(7)]alpha-MSH(3-13) (DOTA-ReCCMSH). METHODS: DOTA-ReCCMSH was compared with its reduced nonmetalated linear homolog, DOTA-CCMSH, and an analog in which rhenium cyclization was replaced by disulfide bond cyclization, DOTA-[Cys(4,10),D-Phe(7)]alpha-MSH(4-13) (CMSH). DOTA was also conjugated to the amino terminus of one of the highest-affinity alpha-MSH receptor-binding peptides, [Nle(4),D-Phe(7)]alpha-MSH (NDP), as a linear peptide standard. The DOTA-conjugated alpha-MSH analogs were radiolabeled with (111)In and examined for their in vitro receptor-binding affinity with B16/F1 murine melanoma cells, and their in vivo biodistribution properties were evaluated and compared in melanoma tumor-bearing C57 mice. RESULTS: The tumor uptake values of (111)In-DOTA-ReCCMSH were significantly higher than those of the other closely related (111)In-DOTA-alpha-MSH conjugates. Even at 24 h after injection, a comparison of the tumor uptake values for (111)In-DOTA-coupled ReCCMSH (4.86 +/- 1.52 percentage injected dose [%ID]/g), CCMSH (1.91 +/- 0.56 %ID/g), CMSH (3.09 +/- 0.32 %ID/g), and NDP (2.47 +/- 0.79 %ID/g) highlighted the high tumor retention property of ReCCMSH. Rhenium-coordinated cyclization resulted in less renal radioactivity accumulation of (111)In-DOTA-ReCCMSH (8.98 +/- 0.82 %ID/g) than of (111)In-DOTA-CCMSH (63.2 +/- 15.6 %ID/g), (111)In-DOTA-CMSH (38.4 +/- 3.6 %ID/g), and (111)In-DOTA-NDP (12.0 +/- 1.96 %ID/g) at 2 h after injection and significantly increased its clearance into the urine (92 %ID at 2 h after injection). A high radioactivity uptake ratio of tumor to normal tissue was obtained for (111)In-DOTA-ReCCMSH (e.g., 489, 159, 100, and 49 for blood, muscle, lung, and liver, respectively, at 4 h after injection). CONCLUSION: The novel ReO-coordinated cyclic structure of DOTA-ReCCMSH contributes significantly to its enhanced tumor-targeting and renal clearance properties and makes DOTAReCCMSH an excellent candidate for melanoma radiodetection and radiotherapy.

Animals↗

PubMed2001

Evolution of chinook salmon (Oncorhynchus tshawytscha) populations in New Zealand: pattern, rate, and process.

Chinook salmon, Oncorhynchus tshawytscha, from the Sacramento River, California, USA were introduced to New Zealand between 1901 and 1907, and colonized most of their present-day range within about 10 years. The New Zealand populations now vary in phenotypic traits typically used to differentiate salmon populations within their natural range: growth in freshwater and at sea, age at maturity, dates of return to fresh water and reproduction, morphology, and reproductive allocation. This paper reviews a large research program designed to determine the relative contributions of phenotypic plasticity and genetic adaptation to this variation, in an effort to understand the processes underlying the natural evolution of new populations. We found strong evidence of trait divergence between populations within at most 30 generations, particularly in freshwater growth rate, date of return, and reproductive output, with plausible adaptive bases for these differences. Importantly, we also demonstrated not only a genetic basis for post-release survival but higher survival, and hence fitness, of a population released from its established site compared to another population released from the same site. We conclude that divergence of salmon in different rivers probably resulted initially from phenotypic plasticity (e.g., habitat-specific growth rates, and effects of upriver migration on ovarian investment). Philopatry (homing to natal streams) combined with rapid evolution of distinct breeding periods to restrict gene flow, facilitating divergence in other traits. We also suggest that in addition to genetic divergence resulting from random founder effects, divergence may also arise during the very early stages of colonization when the original colonists are a non-random, pre-adapted subset of the source population. This 'favored founders effect' immediately improves the fitness of the new population. Overall, this research reveals the complex interplay of environmental and genetic controls over behavior, physiology and life history that characterize the early stages of population differentiation, a process that has taken place repeatedly during the history of salmon populations.

Adaptation, Biological↗

PubMed2000

Rapid evolution of reproductive isolation in the wild: evidence from introduced salmon.

Colonization of new environments should promote rapid speciation as a by-product of adaptation to divergent selective regimes. Although this process of ecological speciation is known to have occurred over millennia or centuries, nothing is known about how quickly reproductive isolation actually evolves when new environments are first colonized. Using DNA microsatellites, population-specific natural tags, and phenotypic variation, we tested for reproductive isolation between two adjacent salmon populations of a common ancestry that colonized divergent reproductive environments (a river and a lake beach). We found evidence for the evolution of reproductive isolation after fewer than 13 generations.

Alleles↗

PubMed2000

Melanoma-targeting properties of (99m)technetium-labeled cyclic alpha-melanocyte-stimulating hormone peptide analogues.

Preliminary reports have demonstrated that (99m)technetium (Tc)-labeled cyclic [Cys(3,4,10), D-Phe7]alpha-MSH(3-13) (CCMSH) exhibits high tumor uptake and retention values in a murine melanoma mouse model. In this report, the tumor targeting mechanism of 99mTc-CCMSH was studied and compared with four other radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) peptide analogues: 125I-(Tyr2)-[Nle4, D-Phe7]alpha-MSH [125I-(Tyr2)-NDP]; 99mTc-CGCG-NDP; 99mTc-Gly11-CCMSH; and 99mTc-Nle11-CCMSH. In vitro receptor binding, internalization, and cellular retention of radiolabeled alpha-MSH analogues in B16/F1 murine cell line demonstrated that >70% of the receptor-bound radiolabeled analogues were internalized together with the receptor. Ninety % of the internalized 125I-(Tyr2)-NDP, whereas only 36% of internalized 99mTc-CCMSH, was released from the cells into the medium during a 4-h incubation at 37 degrees C. Two mouse models, C57 mice and severe combined immunodeficient (Scid) mice, inoculated s.c. with B16/F1 murine and TXM-13 human melanoma cells were used for the in vivo studies. Tumor uptake values of 11.32 and 2.39 [% injected dose (ID)/g] for 99mTc-CCMSH at 4 h after injection, resulted in an uptake ratio of tumor:blood of 39.0 and 11.5 in murine melanoma-C57 and human melanoma-Scid mouse models, respectively. Two strategies for decreasing the nonspecific kidney uptake of 99mTc-CCMSH, substitution of Lys11 in CCMSH with Gly11 or Nle11, and lysine coinjection, were evaluated. The biodistribution data for the modified peptides showed that Lys11 replacement dramatically decreased the kidney uptake, whereas the tumor uptakes of 99mTc-Nle11- and 99mTc-Gly11-CCMSH were significantly lower than that of 99mTc-CCMSH. Lysine coinjection significantly decreased the kidney uptake (e.g., from 14.6% ID/g to 4.5% ID/g at 4 h after injection in murine melanoma-C57 mice) without significantly changing the value of tumor uptake of 99mTc-CCMSH. In conclusion, the compact cyclic structure of 99mTc-CCMSH, its resistance to degradation, and its enhanced intracellular retention are the major contributing factors to the superior in vivo tumor targeting properties of 99mTc-CCMSH. Lys11 residue in 99mTc-CCMSH is critical to the tumor targeting in vivo, and lysine coinjection rather than lysine replacement can significantly decrease the nonspecific renal radioactivity accumulation without impeding the high melanoma-targeting properties of 99Tc-CCMSH. The metal-cyclized CCMSH molecule displays excellent potential for the development of melanoma-specific diagnostic and therapeutic agents.

Amino Acid Sequence↗

PubMed2000

Effects of Thomsen-Friedenreich antigen-specific peptide P-30 on beta-galactoside-mediated homotypic aggregation and adhesion to the endothelium of MDA-MB-435 human breast carcinoma cells.

Both the ability of malignant cells to form multicellular aggregates via homotypic or heterotypic aggregation and their adhesion to the endothelium are important if not critical during early stages of cancer metastasis. The tumor-associated carbohydrate Thomsen-Friedenreich antigen (T antigen) and beta-galactoside binding lectins (galectins) have been implicated in tumor cell adhesion and tissue invasion. In this study, we demonstrate the involvement of T antigen in both homotypic aggregation of MDA-MB-435 human breast carcinoma cells and their adhesion to the endothelium. The T antigen-specific peptide P-30 (HGRFILPWWYAFSPS) selected from a bacteriophage display library was able to inhibit spontaneous homotypic aggregation of MDA-MB-435 cells up to 74% in a dose-dependent manner. Because T antigen has beta-galactose as a terminal sugar, the expression profile of beta-galactoside-binding lectins (galectins) in MDA-MB-435 cells was studied. Our data indicated the abundant expression of [35S]methionine/cysteine-labeled galectin-1 and galectin-3 in this cell line, which suggested possible interactions between galectins and T antigen. As revealed by laser confocal microscopy, both galectin-1 and galectin-3 also participate in the adhesion of the MDA-MB-435 cells to the endothelium. We observed the clustering of galectin-3 on endothelial cells at the sites of the contact with tumor cells, consistent with its possible interaction with T antigen on cancer cells The galectin-1 signal, however, strongly accumulated at the sites of cell-cell contacts predominantly on tumor cells. The T antigen-specific P-30 significantly (50%) inhibited this adhesion, which indicated that T antigen participates in the adhesion of MDA-MB-435 breast cancer cells to the endothelium. The ability of synthetic P-30 to inhibit both the spontaneous homotypic aggregation of MDA-MB-435 cells and their adhesion to the endothelium (>70 and 50%, respectively) suggests its potential functional significance for antiadhesive therapy of cancer metastasis.

Amino Acid Sequence↗

PubMed2000

Evolution of temporal isolation in the wild: genetic divergence in timing of migration and breeding by introduced chinook salmon populations.

The timing of migration and breeding are key life-history traits; they are not only adaptations of populations to their environments, but can serve to increase reproductive isolation, facilitating further divergence among populations. As part of a study of divergence of chinook salmon, Oncorhynchus tshawytscha, populations, established in New Zealand from a common source in the early 1900s, we tested the hypotheses that the timing of migration and breeding are under genetic control and that the populations genetically differ in these traits despite phenotypic overlap in timing in the wild. Representatives of families from two populations were collected within a day or two of each other, reared in a common environment, and then released to sea from each of two different rivers, while other family representatives were retained in fresh water to maturity. The date of maturation of fish held in fresh water and the dates of return from the ocean and maturation of fish released to sea all showed significant differences between the two populations and among families within populations. The very high heritabilities and genetic correlations estimated for migration and maturation date indicated that these traits would respond rapidly to selection. Combined with the results of related studies on these chinook salmon populations, it appears that spawning time may not only evolve during the initial phases of divergence, but it may play an important role in accelerating divergence in other traits.

Animals↗

PubMed1999

Vascular endothelial growth factor-induced migration of vascular smooth muscle cells in vitro.

Angiogenesis is a complex process that includes recruitment and proliferation of mural cells-smooth muscle cells (SMC) and pericytes. Vascular endothelial growth factor (VEGF) has been shown to play an important role in angiogenesis and is an endothelial cell chemoattractant. In addition, certain VEGF isoforms have been implicated in the normal formation of smooth muscle cell-surrounded arteries. Because VEGF's role as a mural cell chemoattractant had not been explored, we examined the ability of VEGF to influence vascular SMC migration in vitro. A Boyden chamber migration assay demonstrated that VEGF (0-100 ng/ml) caused a dose-dependent migration of SMC. VEGF did not cause proliferation of SMC. Reverse transcriptase-polymerase chain reaction analysis demonstrated the presence of both KDR and flt mRNA, two known VEGF receptors, in SMC cultures. Western blot analysis of SMC lysates confirmed these data, revealing bands migrating at approximately 200 kDa and slightly below 200 kDa consistent with KDR and flt. These observations demonstrate that VEGF receptors are present on SMC, and that VEGF can act as an SMC chemoattractant.

Animals↗

PubMed1999

Analysis of T cell receptors specific for U1-70kD small nuclear ribonucleoprotein autoantigen: the alpha chain complementarity determining region three is highly conserved among connective tissue disease patients.

The U1-70kD autoantigen is a major target of B cell responses in patients with connective tissue diseases (CTD). T cell responses are important in the pathogenesis of CTD, however little is known about autoantigen-specific T cells in these diseases. We have recently proven that U1-70kD-reactive human T cells exist. To further characterize these autoreactive T cells, U1-70kD-reactive T cell clones have been generated from patients with CTD using either a recombinant fusion protein or synthetic peptides spanning the U1-70kD polypeptide. T cell receptors (TCR) isolated from the U1-70kD-reactive T cell clones were sequenced and the third complementarity-determining region (CDR3) compared to determine if a common motif was present. mAb blocking of antigen-induced proliferation was done to determine the HLA restriction element used in recognition of the U1-70kD autoantigen by T cells. The results presented here indicate that TCRAV CDR3 usage is highly restricted among U1-70kD autoantigen-specific human T cells clones derived from CTD patients with distinctive structural features. Furthermore, the recognition of the U1-70kD autoantigen occurs in the context of HLA-DR.

Amino Acid Sequence↗