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Cell-mediated immunity directed against human papillomavirus 16 (HPV-16) antigens was studied in 16 patients affected with classic vulvar intra-epithelial neoplasia (VIN), also known as bowenoid papulosis (BP). Ten patients had blood lymphocyte proliferative T cell responses directed against E6/2 (14–34) and/or E6/4 (45–68) peptides, which were identified in the present study as immunodominant among HPV-16 E6 and E7 large peptides. Ex vivo enzyme-linked immunospot–interferon (IFN)-γ assay was positive in three patients who had proliferative responses. Twelve months later, proliferative T cell responses remained detectable in only six women and the immunodominant antigens remained the E6/2 (14–34) and E6/4 (45–68) peptides. The latter large fragments of peptides contained many epitopes able to bind to at least seven human leucocyte antigen (HLA) class I molecules and were strong binders to seven HLA-DR class II molecules. In order to build a therapeutic anti-HPV-16 vaccine, E6/2 (14–34) and E6/4 (45–68) fragments thus appear to be good candidates to increase HPV-specific effector T lymphocyte responses and clear classic VIN (BP) disease lesions. [ABSTRACT FROM AUTHOR]

It has been reported that autoantibodies against the β2-adrenergic receptors are involved in the pathology of allergic disorders and of Chagas' disease. Therefore, the immune response against a peptide (H26Q) corresponding to the putative second extracellular loop of the human β2-adrenergic receptor, which could be a target for autoantibody attack, was analysed in view of its possible immunogenicity. The free peptide induced a T cell-mediated humoral response in the context of three different murine MHC haplotypes. The T cell epitope was found to be localized in the N-terminal region of the peptide. Highly specific T helper cells were capable of stimulating B cells with the potential to generate a large antibody repertoire reactive with the loop peptide. MoAbs were screened to analyse this B cell response for antibodies potentially interfering with receptor function and a MoAb was found that impaired ligand binding to the receptor. [ABSTRACT FROM AUTHOR]

Polyclonal antibodies were raised in rabbits by immunization with free peptides corresponding to positions 197-222 of the human β1-adrenergic receptor (β1 peptide) and the corresponding sequence (172-197) of the human β2-adrenergic receptor (β2 peptide). While the β2 peptide yielded antibodies that cross-reacted with the β1 peptide, the antibodies against the β1 peptide did not cross-react with the β2 sequence. Cross-reactivity of the anti-β2 peptide antibodies and the selectivity of the anti-β1 peptide antibodies were also revealed in the recognition by immunoblots of the β1- and β2-adrenergic receptors of different species or of the receptor gene products expressed in a bacterial vector. These antibodies could be used immunohistochemically to visualize the β-adrenergic receptors on rabbit heart. The anti-β2 peptide antibodies did not show any functional effect on the β-adrenergic receptors; the anti-β1 peptide antibodies were able to displace agonist affinity to higher values. Recognition of truncated peptides by the anti-β1 and anti-β2 peptide antibodies suggested that the cross-reaction of the anti-β2 peptide antibodies was due to the recognition of a common epitope on the C-terminal part of the peptides. The anti-β1 peptide antibodies recognized the N-terminal part of the peptide better than the C-terminal part. These results suggest that the second extracellular loop postulated in the structure of the human β-adrenergic receptor contains the T and B cell epitopes necessary for induction of an immune response. The selectivity and the functional properties of the antibodies raised against that loop in the β1 adrenergic receptor could have relevance in induction of auto antibodies in certain cardiomyopathic conditions. [ABSTRACT FROM AUTHOR]