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At least 1,693 records · Page 94Linked to original sources
PubMed2002

Novel cost-effective method of screening soils for the presence of mosquito-pathogenic bacilli.

AIMS: The aim was to simplify the cumbersome conventional process of isolating virulent bacilli, which involves isolating all bacilli strains from a source followed by screening for strains that are effective for bio-control of mosquito vectors. METHODS: A new simplified technique involving eight steps was devised for screening soil samples for the presence of mosquito-pathogenic bacilli before isolating individual strains. RESULTS: Using the new technique, we obtained eight bacilli strains (KSD1-8) showing pathogenic activity against mosquito larvae from three out of 10 soil samples screened. These strains were characterized, identified and the main bioassay tests were performed with three most promising strains (KSD-4, KSD-7 and KSD-8), and their pathogenic activity against Anopheles stephensi Liston, Culex quinquefasciatus, Say and Aedes aegypti Linnaeus compared well with commercial reference strains of B. thuringiensis israelensis and B. sphaericus. SIGNIFICANCE AND IMPACT OF THE STUDY: The new technique of screening soil samples for the presence of virulent pathogenic strains of bacilli against mosquito larvae proved quick, efficient and cost effective.

Animals↗
PubMed2002

Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma.

BACKGROUND: Therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (TSE) transmission. Previously, hamster-adapted scrapie was used as a model agent to assess TSE clearance in purification steps leading to the isolation of biopharmaceutical proteins. The current study investigated the validity of hamster scrapie as a model for human TSE clearance studies. The partitioning of the pathogenic forms of the prion protein associated with human variant CJD (PrP(vCJD)), human sporadic CJD (PrP(sCJD)) and Gerstmann-Sträussler-Scheinker (PrP(GSS)) syndrome was compared to the partitioning of hamster scrapie (PrP(Sc)) in three plasma protein purification steps. Sheep scrapie (PrP(Sc)) was similarly evaluated. STUDY DESIGN AND METHODS: The starting materials for three plasma protein purification steps, cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation, were spiked with brain homogenates containing human PrP(vCJD), human PrP(sCJD), human PrP(GSS), sheep PrP(Sc), and hamster 263K PrP(Sc). The partitioning of the pathogenic form of the PrP was analyzed. RESULTS: Clearance of the pathogenic form of the PrP was measured relative to the effluent fraction. Regardless of the source of the pathogenic prion, clearance was similar to hamster PrP(Sc). A nominal amount of clearance (approx., 1 log), an intermediate amount of clearance (approx., 2 log), and a substantial amount of clearance (> or = 3 log) were observed for the cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation steps, respectively. In the latter step, no PrP was detected in the effluents. CONCLUSIONS: These data demonstrate that human prions, including vCJD prions, can be removed during the purification of human therapeutic proteins and indicate that partitioning of human prions is similar to that observed in the hamster scrapie model.

Animals↗
PubMed2000

New technologies for the inactivation of infectious pathogens in cellular blood components and the development of platelet substitutes.

Despite the increased safety of blood components, achieved through improved donor selection and testing, transfusion recipients remain at risk of transfusion-associated diseases. Transfusion of cellular blood components has been implicated in transmission of viral, bacterial and protozoan diseases. While it is commonly recognized that hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), and retroviruses, such as human immunodeficiency virus (HIV) and the human lymphotrophic viruses (HTLV), can be transmitted through cellular components, other pathogens are emerging as potentially significant transfusion-associated infectious agents. For example, transmission of protozoan infections due to trypanosomes and Babesia have been reported. In addition to viral and protozoan infectious agents, cases of bacterial contamination of platelet and red cell concentrates continue to be reported and may be an under-reported transfusion complication. More importantly, new infectious agents continue to enter the donor population, and there is an inherent time delay before the new pathogens are definitively identified and new tests implemented in order to maintain consistent safety of the blood supply. The paradigm for this problem is the HIV pandemic. During the past decade a number of methods for inactivating infectious pathogens in platelet concentrates have been investigated as a strategy to improve the safety of platelet transfusion therapy. One method of treating platelet concentrates to inactive pathogens has now reached the advanced clinical trial phase in the United States and Europe. Similar efforts with a new class of compounds are underway for red cell concentrates, and two of these are in early phase trials. In addition to studies with allogeneic platelets and red cells, a number of laboratories have described methods for developing platelet substitutes or modified platelets to avoid the use of traditional platelet concentrates as a means to improve safety.

Anti-Infective Agents↗
PubMed2000

Antimicrobial susceptibility patterns of respiratory pathogens--a global perspective.

Antimicrobial resistance among respiratory tract pathogens poses a major challenge for the ongoing use of antimicrobial agents for treating infected patients. Global antimicrobial susceptibility data has documented the existence of widespread resistance issues. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis constitute the principal community-acquired respiratory tract bacterial pathogens. For H. influenzae, resistance to ampicillin varies from less than 5% in some European countries to greater than 30% in North America and Southeast Asia. For H. influenzae, resistance to trimethoprim/sulfamethoxazole has been shown to range from less than 5% in North America and Europe to greater than 25% in Europe, the Middle East, and India. For M. catarrhalis, 85% to 100% of isolates worldwide are beta-lactamase positive and, therefore, ampicillin and amoxicillin resistant. Penicillin-resistant S. pneumoniae shows considerable variability worldwide ranging from 6% to 80% whereas macrolide resistance among the pneumococci range from 0% to 90%. Clearly, documenting and understanding the emergence, dissemination, and infection with pathogens resistant to antimicrobial agents is essential for developing strategies to deal with this global problem. This article highlights the frequency of antimicrobial resistance among the respiratory pathogens from a global perspective. Also, mechanisms of resistance and factors associated with the emergence, dissemination, and colonization of resistant organisms are discussed.

Drug Resistance, Microbial↗
PubMed1978

IgA protease production as a characteristic distinguishing pathogenic from harmless neisseriaceae.

IgA proteases are extracellular enzymes of bacteria that have human immunoglobulin A of the IgA1 subclass as their only known substrate. The identification of this enzyme in neisseria prompted us to determine whether IgA protease production correlates with pathogenicity within this genus. Multiple clinical isolates of Neisseria gonorrhoeae, N. meningitidis and eight species of non-pathogenic neisseria that commonly colonize the normal human nasopharynx were examined for IgA protease activity. All N. gonorrhoeae and N. meningitidis strains were enzyme positive; all non-pathogenic strains were negative. Among meningococci, the enzyme occurred in strains carried harmlessly in the nasopharynx as well as those isolated from systemic infections. Because mucosal immune defense is largely mediated by antibodies of the IgA isotype, the finding that IgA protease activity is linked specifically to the pathogenic neisseria suggests that the enzyme may be involved in the pathogenesis of neisserial infection.

Gonorrhea↗
PubMed2001

Ensuring the pathogen safety of intravenous immunoglobulin and other human plasma-derived therapeutic proteins.

Countless patients and clinicians rely on therapeutic proteins, such as intravenous immunoglobulins (IVIGs), isolated from human blood plasma. Since plasma is predisposed to contamination by a variety of blood-borne pathogens, ascertaining and ensuring the pathogen safety of plasma-derived therapeutics is a priority among manufacturers. Even though the pathogen safety records for IVIG and other plasma proteins are excellent, the industry remains active in research programs aimed at improving the margin of safety. Industry initiatives designed to increase the safety of plasma-derived products range from donor screening and testing to implementing methods into the manufacturing processes that can inactivate or remove pathogens from product streams. In general, the industry's comprehensive strategy is designed to provide patients and caregivers with the safest plasma products possible.

Bacteria↗
PubMed2001

An emergency department-based randomized trial of nonbronchoscopic bronchoalveolar lavage for early pathogen identification in severe community-acquired pneumonia.

STUDY OBJECTIVES: Many patients with community-acquired pneumonia are treated empirically without an aggressive search for causative pathogens, an approach adopted largely because of the costs and difficulties encountered during efforts to identify the causative organisms. Blood and sputum cultures are not sensitive, and the more invasive techniques of bronchoscopy and lung biopsy are generally time consuming and not cost-effective. The technique of nonbronchoscopic bronchoalveolar lavage (BAL) has been shown to accurately diagnose the causes of nosocomial pneumonia. The purpose of this study was to determine whether an emergency department-based BAL protocol would lead to more frequent isolation of pneumonia pathogens and result in more changes to tailored antibiotic therapy in comparison with standard care. METHODS: We studied all adult patients admitted with a diagnosis of pneumonia who were tracheally intubated and who had obtainable familial consent in the ED of an urban county hospital from March 1998 to October 1999. Exclusions included antibiotic use within the past 5 days, pneumothorax, hemoptysis, or persistent hypoxia using 100% oxygen. Patients were randomized to standard care versus standard care plus BAL. Blood culture specimens were drawn from all patients before the initiation of antibiotics. All other diagnostic tests were ordered at the discretion of treating physicians. BAL fluid, sputum, and blood culture specimens were tracked, and patient antibiotic course was followed to assess any change in regimen. RESULTS: Twenty-six of 64 patients evaluated for study participation met all eligibility criteria; 14 patients received standard care, and 12 patients received standard care plus BAL. Pneumonia pathogens were identified in 10 (83.3%) of 12 patients in the BAL group and in 4 (28.6%) of 14 patients in the standard care group (P =.007). Comparing BAL versus non-BAL groups, there was no significant difference in the likelihood of overall antibiotic regimen changes (P =.149), but there was a difference with regard to antibiotic changes made in patients with positive culture test results (P =.026). No major complications occurred with BAL catheterizations. CONCLUSION: ED-based BAL catheterization allows for early identification of pathogens in severe community-acquired pneumonia, which leads to changes in antibiotic therapy.

Adult↗
PubMed2005

Pathogenic hantaviruses bind plexin-semaphorin-integrin domains present at the apex of inactive, bent alphavbeta3 integrin conformers.

The alphavbeta3 integrins are linked to human bleeding disorders, and pathogenic hantaviruses regulate the function of alphavbeta3 integrins and cause acute vascular diseases. alphavbeta3 integrins are present in either extended (active) or dramatically bent (inactive) structures, and interconversion of alphavbeta3 conformers dynamically regulates integrin functions. Here, we show that hantaviruses bind human alphavbeta3 integrins and that binding maps to the plexin-semaphorin-integrin (PSI) domain present at the apex of inactive, bent, alphavbeta3-integrin structures. Pathogenic hantaviruses [New York-1 virus (NY-1V) and Hantaan virus (HTNV)] bind immobilized beta3 polypeptides containing the PSI domain, and human (but not murine) beta3 polypeptides inhibit hantavirus infectivity. Substitution of human beta3 residues 1-39 for murine beta3 residues directed pathogenic hantavirus infection of nonpermissive CHO cells expressing chimeric alphavbeta3 receptors. Mutation of murine beta3 Asn-39 to Asp-39 present in human beta3 homologues (N39D) permitted hantavirus infection of cells and specified PSI domain residue interactions with pathogenic hantaviruses. In addition, cell-surface expression of alphavbeta3 locked in an inactive bent conformation conferred hantavirus infectivity of CHO cells. Our findings indicate that hantaviruses bind to a unique domain exposed on inactive integrins and, together with prior findings, suggest that this interaction restricts alphavbeta3 functions that regulate vascular permeability. Our findings suggest mechanisms for viruses to direct hemorrhagic or vascular diseases and provide a distinct target for modulating alphavbeta3-integrin functions.

Amino Acid Sequence↗
PubMed2002

Crosstalk among stress responses in plants: pathogen defense overrides UV protection through an inversely regulated ACE/ACE type of light-responsive gene promoter unit.

Plants often have to cope with two or more environmental hazards simultaneously. Such coincidences require instantaneous decisions on relative severity and consequential crosstalk between the respective signaling cascades. Among the frequently encountered threats are pathogen infections and UV irradiation, both of which trigger specifically targeted defense responses by means of changes in gene transcription rates. In Petroselinum crispum, pathogen defense has been shown to be associated with extensive metabolic reprogramming, including strong repression of the UV-protective flavonoid biosynthetic pathway. Here we show that one of the involved genes, encoding acyl-CoA oxidase, responds positively to UV light and negatively to a pathogen-derived elicitor through an inversely regulated promoter unit consisting of two almost identical ACGT-containing elements (ACEs). This unit, when either introduced into an unrelated promoter or generated by mutation of a differently composed unit, confers the same type of response pattern on the recipient genes, confirming its general functionality at a convergence site of two largely distinct signaling pathways. Similarly large, rapid, and partly inverse effects of UV light and elicitor were observed for several mRNAs encoding common plant regulatory factors (CPRFs) that exhibit distinct dimerization and DNA-binding properties. This striking coincidence suggests a major role of common plant regulatory factors in mediating the apparent switch in the function of ACGT-containing elements from positive UV light to negative elicitor or pathogen responsiveness.

Base Sequence↗
PubMed2005

Nef from pathogenic simian immunodeficiency virus is a negative factor for vaccinia virus.

The nef gene of human and simian immunodeficiency viruses (HIV and SIV) is important for pathogenicity and maintenance of high virus loads. We previously reported that recombinant vaccinia viruses (rVVs) expressing nef from attenuated SIVmac1A11 (vNef1A11) produced typical plaques on thymidine kinase-deficient 143B cells, whereas rVVs expressing nef derived from the pathogenic SIVmac239 (vNef157) formed plaques with altered morphology. Here, we show that vNef157 is attenuated in normal and nude mice, whereas the pathogenicity of vNef1A11 is similar to that of a control virus. Thus, Nef157 is an attenuating factor in the vaccinia virus (VV) system, contrasting sharply with its function in lentiviruses. We also show that Nef157 inhibits VV cell-to-cell spread, causing formation of atypical plaques regardless of thymidine kinase deficiency, neoplasticity, and species of the infected cell line. We hypothesized that Nef157 interferes with VV spread by association with actin, but no direct colocalization of Nef and the cytoskeletal actin network was detected. Instead, higher levels of Nef157 protein were observed, although mRNAs for both nef genes were produced at comparable levels. Thus, the mechanism behind such Nef157 protein accumulation and Nef157-mediated VV attenuation could be related to the process that causes an opposite effect in its native SIV system, making SIVmac239 more pathogenic than SIVmac1A11.

Actins↗
PubMed2005

Microarray-based detection of genetic heterogeneity, antimicrobial resistance, and the viable but nonculturable state in human pathogenic Vibrio spp.

The morbidity and mortality associated with Vibrio-mediated waterborne diseases necessitates the development of sensitive detection technologies that are able to elucidate the identity, potential pathogenicity, susceptibility, and viability of contaminating bacteria in a timely manner. For this purpose, we have designed a single multiplex PCR assay to simultaneously amplify 95 diagnostic regions (encompassing species/serogroup-specific, antimicrobial resistance, and known toxin markers) and combined it with a long oligonucleotide microarray to create a platform capable of rapidly detecting and discriminating the major human pathogenic species from the genus Vibrio: V. cholerae, V. parahaemolyticus, V. vulnificus, and V. mimicus. We were able to validate this strategy by testing 100 geographically and temporally distributed isolates and observed an excellent concordance between species- and serotype-level microarray-based identification and traditional typing methods. In addition to accurate identification, the microarray simultaneously provided evidence of antibiotic resistance genes and mobile genetic elements, such as sulfamethoxazole-trimethoprim constins and class I integrons, and common toxin (ctxAB, rtxA, hap, hlyA, tl, tdh, trh, vvhA, vlly, and vmhA) and pathogenicity (tcpA, type III secretion system) genes that are associated with pathogenic Vibrio. The versatility of this method was further underscored by its ability to detect the expression of known toxin and virulence genes from potentially harmful viable but nonculturable organisms. The results suggest that this molecular identification method provides rapid and definitive information that would be of value in epidemiological, environmental, and health risk assessment surveillance.

Anti-Infective Agents↗
PubMed2006

Interaction between the membrane protein of a pathogen and insect microfilament complex determines insect-vector specificity.

Many insect-transmissible pathogens are transmitted by specific insect species and not by others, even if they are closely related. The molecular mechanisms underlying such strict pathogen-insect specificity are poorly understood. Candidatus Phytoplasma asteris, OY strain, line W (OY), is a phytopathogenic bacterium transmitted from plant to plant by sap-feeding insect vectors (leafhoppers). Our study focused on an abundant cell-surface membrane protein of the phytoplasma named antigenic membrane protein (Amp), which is not homologous with any reported functional protein. Immunofluorescence microscopy of the phytoplasma-infected insect showed that OY phytoplasma was localized to the microfilaments of the visceral smooth muscle surrounding the insect's intestinal tract. The affinity column assay showed that Amp forms a complex with three insect proteins: actin, myosin heavy chain, and myosin light chain. Amp-microfilament complexes were detected in all OY-transmitting leafhopper species, but not in the non-OY-transmitting leafhoppers, suggesting that the formation of the Amp-microfilament complex is correlated with the phytoplasma-transmitting capability of leafhoppers. Although several studies have reported interactions between pathogens and mammalian microfilaments, this is an example of host-specific interactions between a bacterial surface protein and a host microfilament in insect cells. Our data also suggest that the utilization of a host microfilament may be a universal system for pathogenic bacteria infecting mammals or insects.

Actin Cytoskeleton↗
PubMed2006

Changing green leaf volatile biosynthesis in plants: an approach for improving plant resistance against both herbivores and pathogens.

Green leaf volatiles (GLVs) are commonly emitted by green plants, and their production is drastically enhanced when they are under biotic stress. To clarify the ecological function of naturally emitted GLVs, we studied the response of Arabidopsis, whose GLV biosynthesis had been modified, when subjected to herbivory or a pathogenic infection. There was a significant increase in GLV production after herbivory by cabbage white butterfly larvae and pathogen (gray mold) infection in hydroperoxide lyase (HPL) sense Arabidopsis compared with WT controls. The HPL sense modification resulted in the plant being more attractive to the parasitic wasp Cotesia glomerata, leading to higher mortality of the herbivores. The HPL sense modification also resulted in greater inhibition of growth of the fungus. By contrast, HPL antisense Arabidopsis produced fewer GLVs, attracted fewer parasitoids, and was more susceptible to the pathogens than the WT control. These data show that (i) one of the ecological functions of GLV biosynthesis related to resistance against both herbivores and pathogens, and (ii) the genetic modification of GLV biosynthesis could be a unique approach for improving plant resistance against such biotic stresses.

Aldehyde-Lyases↗
PubMed2006

Environmental change and infectious disease: how new roads affect the transmission of diarrheal pathogens in rural Ecuador.

Environmental change plays a large role in the emergence of infectious disease. The construction of a new road in a previously roadless area of northern coastal Ecuador provides a valuable natural experiment to examine how changes in the social and natural environment, mediated by road construction, affect the epidemiology of diarrheal diseases. Twenty-one villages were randomly selected to capture the full distribution of village population size and distance from a main road (remoteness), and these were compared with the major population center of the region, Borbón, that lies on the road. Estimates of enteric pathogen infection rates were obtained from case-control studies at the village level. Higher rates of infection were found in nonremote vs. remote villages [pathogenic Escherichia coli: odds ratio (OR) = 8.4, confidence interval (CI) 1.6, 43.5; rotavirus: OR = 4.0, CI 1.3, 12.1; and Giardia: OR = 1.9, CI 1.3, 2.7]. Higher rates of all-cause diarrhea were found in Borbón compared with the 21 villages (RR = 2.0, CI 1.5, 2.8), as well as when comparing nonremote and remote villages (OR = 2.7, CI 1.5, 4.8). Social network data collected in parallel offered a causal link between remoteness and disease. The significant and consistent trends across viral, bacterial, and protozoan pathogens suggest the importance of considering a broad range of pathogens with differing epidemiological patterns when assessing the environmental impact of new roads. This study provides insight into the initial health impacts that roads have on communities and into the social and environmental processes that create these impacts.

Diarrhea↗
PubMed1983

Characterization of an antigenic determinant of the glycoprotein that correlates with pathogenicity of rabies virus.

The pathogenicity of fixed rabies virus strains for adult mice depends on the presence of an antigenic determinant on the viral glycoprotein. Two virus-neutralizing monoclonal antibodies have been used to identify this determinant. All pathogenic strains of fixed rabies virus bind to these antibodies and are neutralized by them, whereas nonpathogenic strains fail to react with these monoclonal antibodies and are not neutralized by them. Antigenic variants of the rabies virus with altered glycoprotein were selected by growing virus in the presence of one monoclonal antibody, 194-2. All variants that lost their ability to react with this antibody and an additional antibody, 248-8, were found to be nonpathogenic for adult mice. Analysis of tryptic peptides of the glycoproteins of pathogenic parent virus and nonpathogenic variants and the amino acid sequence of a specific variant tryptic peptide revealed that the change in pathogenicity corresponded to an amino acid substitution at position 333 of the glycoprotein molecule. The nucleotide sequence of the nonpathogenic variant glycoprotein gene contained a base change that confirmed the single amino acid substitution in the tryptic peptide replacing arginine-333 in the parental glycoprotein. We conclude that arginine-333 is essential for the integrity of an antigenic determinant and for the ability of rabies viruses to produce lethal infection in adult mice.

Amino Acid Sequence↗
PubMed1988

Pathogenic and host range determinants of the feline aplastic anemia retrovirus.

Feline leukemia virus (FeLV) C-Sarma (or FSC) is a prototype of subgroup C FeLVs, which induce fatal aplastic anemia in outbred specific-pathogen-free (SPF) cats. FeLV C isolates also possess an extended host range in vitro, including an ability, unique among FeLVs, to replicate in guinea pig cells. To identify the viral determinants responsible for the pathogenicity and host range of FSC we constructed a series of proviral DNAs by exchanging gene fragments between FSC and FeLV-61E (or F6A), the latter of which is minimally pathogenic and whose host range in vitro is restricted to feline cells. Transfer of an 886-base-pair (bp) fragment of FSC, encompassing the codons for 73 amino acids at the 3' end of pol (the integrase/endonuclease gene) and the codons for 241 amino acids of the N-terminal portion of env [the extracellular glycoprotein (gp70) gene], into the F6A genome was sufficient to confer onto chimeric viruses the ability to induce fatal aplastic anemia in SPF cats. In contrast, no chimera lacking this sequence induced disease. When assayed in vitro, all chimeric viruses containing the 886-bp fragment of FSC acquired the ability to replicate in heterologous cells, including dog and guinea pig cells. Thus, the pathogenic and the host range determinants of the feline aplastic anemia retrovirus colocalize to a 3' pol-5' env region of the FSC genome and likely reside within a region encoding 241 amino acid residues of the N terminus of the extracellular glycoprotein.

Anemia, Aplastic↗
PubMed1989

Coevolution of host and pathogen populations in the Hordeum vulgare-Rhynchosporium secalis pathosystem.

Isolates of Rhynchosporium secalis collected from two experimental barley populations were scored for putative isozyme, colony color, and virulence loci. Allelic frequencies, multilocus haplotype frequencies, and multilocus genetic structure differed in the two populations of R. secalis; haplotypes also differed widely from each other in virulence. The average virulence of isolates collected from the more resistant host population was greater than the average virulence of the isolates collected from the less resistant host population; also the least virulent haplotype, which made up 19% of the pathogen population collected from the less resistant host population, accounted for only 0.3% of the isolates collected from the more resistant host population. It was concluded that the genetic systems of the barley host and fungal pathogen interacted in a complementary fashion and that the genetic structures of both the host and pathogen populations were shaped by coevolutionary processes featuring interactions among loci affecting many different traits, including interactions among host resistance genes and pathogen virulence genes.

Biological Evolution↗
PubMed1991

Junctional region sequences of T-cell receptor beta-chain genes expressed by pathogenic anti-DNA autoantibody-inducing helper T cells from lupus mice: possible selection by cationic autoantigens.

We rescued from the spleens of 10 (SWR x NZB)F1 (SNF1) mice with lupus nephritis the T cells that were activated in vivo and cloned 268 T-cell lines and hybridomas. Only 12% of these T-cell clones had the functional ability to preferentially augment the production of pathogenic anti-DNA autoantibodies. Among these, 16 helper T-cell (Th-cell) clones that were mostly CD4+ and had the strongest autoantibody-inducing ability were analyzed for T-cell receptor (TCR) beta-chain gene usage. Seven of the 16 Th-cell clones expressed beta-chain variable region (V beta) V beta 8 (8.2 or 8.3) genes and three expressed V beta 4, whereas two clones each used a V beta 1 or V beta 2 or V beta 14 gene, suggesting some restriction in TCR gene usage. Although heterogeneous, the V-D-J junctional region sequences of TCR beta-chain genes used by these Th-cell clones invariably encoded one or more negatively charged residues (aspartic or glutamic acid) that had been generated in most cases by unspecified nucleotide (N) additions. Representative pathogenic autoantibody-inducing Th-cell clones could rapidly induce the development of lupus nephritis when injected into young prenephritic SNF1 mice. The pathogenic autoantibody-inducing Th cells expressing the anionic residues in their TCR beta-chain junctions (complementarity-determining region CDR3) were probably selected by some cationic autoantigenic peptide presented by the anti-DNA B cells they preferentially helped. These results offer a clue regarding the nature of the primary autoantigen that may drive the pathogenic autoimmune response in lupus.

Amino Acid Sequence↗