Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies against capsular polysaccharides are important in the defense against many pathogenic bacteria. To determine the mechanism for the variability in responses to polysaccharides, a panel of well characterized serologic reagents that identify diagnostic primary amino acid sequences in the framework and hypervariable regions of heavy (H) and light (L) chains were created to characterize the variable region diversity in circulating human antibodies. 10 normal adult volunteers were immunized with the type b capsular polysaccharide of Haemophilus influenzae (Hib PS). By immunoblot analyses each individual was found to use at least three different variable L (VL) families, but all had preferential usage of VH3-derived H chains. Four individuals had lesser populations of VH1-derived H chains and three had populations of VH4-derived H chains, but anti-Hib PS antibodies derived from the VH2, VH5, and VH6 families were not detected. The anti-Hib PS antibodies from all subjects were also identified by serologic markers for two specific types of VH3 H chains. These H chains are structurally related to the 20P1 and 30P1 VH genes that are preferentially rearranged in the early human repertoire. These findings document the VH restriction of physiologic responses to Hib PS immunization, and demonstrate a technique to directly assess the structural and genetic diversity of specific serum antibodies.
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PMID:Variable region diversity in human circulating antibodies specific for the capsular polysaccharide of Haemophilus influenzae type b. Preferential usage of two types of VH3 heavy chains. 190 53

Structural analysis of the human immunoglobulin repertoire holds promise for determining the basis of variable region gene usage in response to a variety of auto and exogenous antigens. Here we report the nucleotide sequences of the heavy and light chain variable regions expressed by three human monoclonal antibodies specific for two clinically relevant bacterial pathogens, Bordetella pertussis and Haemophilus influenzae type b. The cell lines were derived by in vitro stimulation of lymphocytes from spleen or tonsillar tissue, respectively, and bind to different antigens from the two organisms. The single B. pertussis antibody is of the IgM lambda isotype and utilizes the single VH6 gene segment in combination with a V lambda 2 gene and demonstrates limited somatic mutation, yet is highly indicative of an antigen-driven immune response. One H. influenzae antibody is of the IgG2 lambda isotype and expresses a VH3 gene segment with a V lambda 1 gene, while the second cell line produces an IgG3 lambda antibody expressing a combination of VH2/V lambda 3. Both molecules show evidence of somatic mutation. The D gene segments of the heavy chains vary in length and display limited sequence homology with known germline D segments. As demonstrated previously, JH4 predominates (two JH4 and one JH3) and all three utilize the J lambda 3 gene segment. In addition, we have isolated and sequenced a number of germline VH2 gene segments in an attempt to better understand the nature of the VH2 germline repertoire. In addition to contributing to the understanding of the human antibody repertoire, such clinically relevant molecules may prove to be a source of passive immunotherapy for those at risk to developing disease.
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PMID:Molecular characterization of human antibodies to bacterial antigens: utilization of the less frequently expressed VH2 and VH6 heavy chain variable region gene families. 824 31