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  • 1
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The grass pollen allergen Lol p III (M r11 000) is a well-characterized antigen that has been found useful in immunogenetic studies of human immune responsiveness. Since immune responsiveness to this allergen is associated with HLA-DR3, we investigated whether there was any sequence in the HLA-D region that would render a person “susceptible” [antibody (Ab)-positive] to the allergen. By sequence-specific oligonucleotide (SSO) slot-blot and sequence analyses of polymerase chain reaction (PCR)-amplified genomic DNA from Lol p III responder and nonresponder subjects, Ab responsiveness was found to be strongly associated with the sequence Glu-Tyr-Ser-Thr-Ser (EYSTS), present in the first polymorphic regions of DRβI polypeptide chains of DR3, DR11 (split of DR5), and DRw6. Of the 41 grass-allergic subjects investigated, 19 had the EYSTS sequence, of whom 18 (95%) were Lol p III immunoglobulin G (IgG) Ab responder; among the 22 EYSTS- subjects, ten were Lol p III responders (P=0.0001, relative risk=21.6). No such association was found with any polymorphic sequences in othe DRβ chains,or in DQαI and DQβI chains. These findings suggest that the EYSTS sequence is important in the presentation of an epitope of Lol p III; other sequence(s) may be involved in the presentation of othe epitope(s). To our knowledge, this is the first demonstration of a strong association between a specific HLA sequence and immune responsiveness to a well-defined antigen. The paper shows that presence of the EYSTS sequence classifies subjects as Lol p III responders in 18/19 cases.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Immunogenetics 35 (1992), S. 421-424 
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 3
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have studied the genetics of human immune response utilizing IgE-mediated allergic response as a model system. Tests performed on unrelated allergic Caucasian subjects revealed a weak association between responsiveness to ragweed pollen allergen Ra3 and HLA-A2 (p=0.04). Most importantly, we observed a relationship between the frequency of HLA-A2 and total serum IgE level in people allergic to Ra3. This frequency was significantly higher in atypical Ra3-sensitive people with low IgE levels of 16–127 U/ml (where over 90 percent possessed A2) than in those with more typical high IgE levels. We postulate that a “majorIr-Ra3+” allele of anIr-Ra3 locus is associated with HLA-A2. Given the natural limiting conditions of exposure to Ra3, we suggest that only thisIr-Ra3+ allele will permit IgE antibody synthesis against Ra3 in allergic subjects with limiting low IgE levels. However, the expression of “minorIr-Ra3+” alleles (of the same or differentIr loci) not associated with A2 may be apparent in Ra3 responders having high IgE levels.
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  • 4
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In 76 members of 13 large families, we investigated whether association exists between specific familialHLA haplotypes and immune responsiveness to four different highly purified pollen antigens (ragweed antigens E, Ra3, and Ra5 and rye grass Group I). Specific immune response was studied quantitatively by measurement of IgE-mediated skin sensitivity, serum IgG antibody, and antigen-induced lymphocyte proliferationin vitro. We found no evidence for association between specificHLA haplotype and specific response measured by any one or more of our indices of immune function. In several families we found evidence of specific response in one generation but not in another. We found a number of instances of individuals exhibiting lymphocyte responsiveness to an antigen, but no detectable specific IgE or IgG antibody. Surprisingly, we also found a few cases of individuals with marked IgE and/or IgG responses to a given antigen who showed no measurable lymphocyte responsiveness to that antigen, despite lymphocyte responsiveness to other nonimmunologically crossreacting antigens. In several cases, we also observed lymphocyte stimulation and serum IgG antibody, but no detectable IgE response. Our results conflict with previous investigators' reports of “linkage” betweenHLA haplotype and specific IgE-mediated skin sensitivity in families.HLA- linked immune response (Ir) loci may exist in humans, but genetic complexity and the limits of current technology preclude our ability to demonstrate their existence.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Immunogenetics 5 (1977), S. 235-251 
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In allergic Caucasian subjects, IgE-mediated responsiveness to the rye grass Group I (Rye I) antigen is significantly associated with possession of HLA-B8 (p = 0.001). Analysis of this association relative to basal total serum IgE level showed a marked relationship in Rye I-negative subjects, where the frequency of B8 was much higher at high than at low IgE levels. In Rye I-positive subjects, there was evidence for the converse situation. In the case of people sensitive to ragweed antigen E, we found no association with any HLA specificity, even in patients with low IgE levels. TheHLA-associated specific IgE responses to rye grass Group I, and those we have previously reported for ragweed Ra3 and Ra5, lead us to speculate about the possible locations within theHLA complex of putativeIr loci controlling recognition of these allergens. Further, we postulate the existence of twoI regions.I-1, which contains “Ir-Rye I” and“Ir-Ra5”, andI-2, which contains “Ir-Ra3”. Alternative explanations of our findings are also discussed in detail.
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  • 6
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Conclusion Finally, in a broader context, part of the fascination of this subject is its relevance to the questions of how responses in the different Ig classes and subclasses are orchestrated, and why such a diversity of Ig classes exists at all. These questions are of great theoretical interest in themselves, and are also highly relevant to those immunological diseases that are characterized by production of auto-or isoantibodies of very restricted subclass (e.g., Karpatkinet al. 1973, Morellet al. 1973) or clonality (e.g., Goldberg and Fudenberg 1971, Harboe 1971, Kunkelet al. 1973). They are also questions that the IgE system—since it is so sophisticated and well-Defined—highlights in a particularly telling way.
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  • 7
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Die verschiedenen chemisch charakterisierten Alkaloide, die in Menispermazeen angetroffen werden, sind auf allfällig nützliche Curarewirkung hin untersucht worden. Bloß diejenigen Verbindungen mit Dibenzyltetrahydroisochinolinstruktur, die zwei Stickstoffatome mit je vier Kovalenzen und eine Elektrovalenz besitzen bzw. in solche Verbindungen umgewandelt werden können, besitzen eine nennenswerte Wirkung. Die zwanzig wirksamen Verbindungen sind auf ihre Fähigkeit, eine Paralyse der Skelettmuskulatur mit minimalen unerwünschten Nebenwirkungen an Ratten, Kaninchen, Katzen, Hunden und Menschen hervorzurufen, untersucht worden. Died-tubocuraringruppe, einschließlich die Curarin-Chondrodendrin-Chondrocurin-Abkömmlinge, besitzt die wirksamsten Verbindungen, weist aber zahlreiche unerwünschte Nebenwirkungen auf. DieN-Methyldauricin-Gruppe, in welcher zwei Benzylisochinolingruppen durch bloß eine Ätherbindung statt zwei verbunden sind, hat die diffuseste cholinergische Histaminwirkung. Die Isochondrodendrinabkömmlinge sind nicht sehr wirksam, haben aber unangenehme Nebenwirkungen. Die Oxyacanthingruppe ist insofern interessant, als alle ihre Glieder, obgleich sie identische Grundformeln besitzen, in ihrer Wirksamkeit und ihren Nebenwirkungen sehr verschieden sind: es gibt hochwirksame Substanzen, die, wieN-Methylberbamin, fast keine Nebenwirkungen haben; oderN-Methyloxyacanthin, welches curariform und schwach atropinähnlich ist; oderN-Methyltetrandrin, welches nikotin- und muscarinähnlich, aber nur schwach curareähnlich ist. Von den übrigen Gruppen sind die ejnzig brauchbaren MitgliederN-Methylcepharanthin undN-Methyltrilobin, außergewöhnlich, indem sie eine erheblich paralysierende, aber fast keine andere Wirkung zeigen.
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  • 8
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Company
    Nature biotechnology 12 (1994), S. 639-640 
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] The Clinton administration' s health-care reform legislation was introduced to Congress in July 1993, as H.R. 2624, H a bill entitled “Comprehensive Health Care and Cost Containment Act of 1993.” Discussions of the impact of that legislation have been widespread and will continue ...
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  • 9
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Company
    Nature biotechnology 11 (1993), S. 937-937 
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] As the editors of Release of Genetically Engineered & Other Micro-organisms, Martin Day and John Fry aim to give their readers a greater understanding of the ecological basis surrounding the release of microorganisms into the environment The strength of this multiauthored book lies in its ...
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  • 10
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature genetics 2 (1992), S. 252-254 
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Atopic allergy is comprised of a wide range of IgE-mediated disorders, which can be provoked by an enormous variety of foreign antigens (allergens). Allergic rhinitis (hay fever), asthma, atopic dermatitis (eczema) and certain types of food allergies are among the most common clinical ...
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