Biomedical subjects
Publications and source records attributed to B Fleckenstein.
Two types of genomes are present in HVS stocks: (1) the defective H-genome consisting of highly reiterated heavy (71% C+G) sequences; and (2) the M-genome, which carries the whole genetic information of HVS and is infectious in tissue culture. The sequences in the M-genome are made up of 70% unique L-DNA (with 36% C + G) and 30% H-DNA, which is highly repetitive. H-sequences in the M-genome are clustered at the ends of the molecule.
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Complete experimental data sets of HLA-ligand motifs and T-cell recognition patterns can be derived from combinatorial peptide libraries. These data provide the exact molecular basis for a fast development of synthetic vaccines, T-cell superagonists and non-peptide antagonists. Patient-specific peptides, peptidomimetics and vaccines of highest reactivity can be derived directly from the data sets via our prediction programme EPIPREDICT. The resulting lead structures may be developed into valuable diagnostics and therapeutic tools for the treatment of viral infections, autoimmune diseases and tumors. As one example, antibody and T cell recognition in the intestinal auto-immune disease, coeliac disease was investigated in more detail concerning the deamidation of gamma-gliadin peptides by tissue transglutaminase 9tTG) leading to autoreactive peptides specific for HLA-DQA1*0501, DQB1*0201.
Human herpesvirus 8 (HHV-8), also termed Kaposi's sarcoma-associated herpesvirus, was identified in Kaposi's sarcoma (KS) biopsy specimens in 1994. The epidemiological data available to date indicate a strong association of HHV-8 with KS. It appears that HHV-8 is necessary for KS development. HHV-8 DNA is invariably found in all epidemiological forms of KS and primary effusion lymphomas. In contrast, HHV-8 DNA is rarely found in various tumor and nontumor tissues from patient groups not at risk of KS. Although current serology does not allow us to assess the HHV-8 prevalence in the general population, high titers of HHV-8 antibodies are almost exclusively found in KS risk groups. In addition, HHV-8 seroconversion has been shown to precede KS development. The mechanisms and genes involved in HHV-8 pathogenesis are less clear. HHV-8 belongs to a family of transforming viruses, and several candidate oncogenes have been identified by using rodent fibroblast transformation assays. However, expression of most of these genes could not be shown in latently infected tumor cells. As the HHV-8 genome encodes several cytokines and cytokine receptor homologues, HHV-8 may also promote KS pathogenesis through paraendocrine mechanisms.
OBJECTIVE: In the oligoarticular subgroup of juvenile idiopathic arthritis, a strong association has been found with the expression of human leukocyte antigen class II molecules HLA-DQA1 *0401-DQB1*0402 and DQA1*0501-DQB1*0301, whereas DQA1*0501-DQB1*0201 is neutral and DQA1 *0201-DQB1*0201 protective. A presentation of different peptides by these DQ alleles would support their role in the disease process. METHODS: Using a synthetic nonapeptide library, a peptide binding motif was determined for the associated DQA1*0501-DQB1*0301 molecule and compared to the neutral and the protective DQ molecules. RESULTS: A differential motif for the three molecules could be deduced, suggesting that peptides preferentially binding to the associated vs. the neutral/protective DQ-molecules are mutually exclusive. CONCLUSION: These results imply a role for differential peptide presentation in the pathogenesis of oligoarthritic JIA. The search for peptides initiating the disease process might be facilitated which could then lead to therapeutical interventions.
Paired sera and CSF samples were collected from SIVmac-infected macaques. Animals infected with SIVmac251 maintained low gag and high env-specific antibody levels in plasma. Increasing env-specific antibody titers in CSF were associated in one animal with strong intrathecal synthesis. SIVmac239-infected monkeys revealed high antibody titers of gag and env-specificity, in one animal accompanied by weak intrathecal synthesis of virus-specific antibodies. In all animals, the CD4/CD8 ratio in CSF decreased faster compared to blood.