Cysteines are thought integral to conformational epitopes of islet antigen-2 (IA-2) autoantibodies (IA-2A), possibly through disulfide bond formation. We therefore investigated which cysteines are critical to IA-2A binding in patients with newly diagnosed type 1 diabetes. All 10 cysteines in the intracellular domain of IA-2 were modified to serine by site-directed mutagenesis, and the effects o...

BACKGROUND CD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens. METHODS The published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were ...

High-titer IgG autoantibodies to the La/SS-B ribonucleoprotein (RNP) are a hallmark of patients with primary Sjogren's syndrome. Anti-La/SS-B-positive human sera bind to multiple epitopes on recombinant La/SS-B, although the initial response is against an immunodominant epitope within the first 107 NH2-terminal amino acids (aa). Sequence analysis has identified a striking homology between aa 88...

Trastuzumab is a growth-inhibitory humanized Ab targeting the oncogenic protein HER-2/neu. Although trastuzumab is approved for treatment of advanced breast cancer, a number of concerns exist with passive immunotherapy. Treatment is expensive and has a limited duration of action, necessitating repeated administrations of the mAb. Active immunotherapy with conformational B cell epitopes affords ...

Thyroid peroxidase (TPO) catalyses the biosynthesis of thyroid hormones and is a major autoantigen in Hashimoto's disease--the most common organ-specific autoimmune disease. Epitope mapping studies have shown that the autoimmune response to TPO is directed mainly at two surface regions on the molecule: immunodominant regions A and B (IDR-A, and IDR-B). TPO has been a major target for structural...

The prevalence of anti-E2 antibody in persons chronically infected with hepatitis C virus (HCV) is high irrespective of viral genotype, and this cross-reactive antibody is thought to react with a conformational epitope. To investigate the characteristics of this anti-E2 antibody, the immunoreactivity of sera from HCV-1b-infected patients was measured against various modified forms of E2 glycopr...

Recombinant Oka (ROka) varicella vaccine expressing hepatitis B surface antigen (HBsAg) and subunit HBsAg vaccine (SHV) were used as primary and booster HBsAg vaccines in 3 combinations (SHV-SHV, SHV-ROka, and ROka-SHV) in guinea pigs. Immune responses to HBsAg and varicella-zoster virus gE:gI were evaluated. The 3 combinations induced similar levels of the lymphocyte proliferation response to ...

As part of the goal of assembling a mixture of neutralizing human mAbs for possible prophylaxis and therapy of HIV-1 disease, we describe a strategy by which neutralizing human Abs to a weakly immunogenic epitope can be accessed. From a phage display library derived from an asymptomatic HIV-1 seropositive donor, a panel of recombinant Fabs against the CD4 binding site (CD4bs) of gp120 was retri...

Hepatitis delta antigen (HDAg) consists of two species, large (LHDAg) and small (SHDAg), which are identical in sequence except that the large form contains 19 extra amino acids at the C terminus. The large form is prenylated on the Cxxx motif. The small form can trans activate HDV RNA replication, while the large form inhibits it. To determine the molecular basis for their differential functio...