Showing papers by "Richard M. Scearce published in 1995"

HIV type 1 V3 region primer-induced antibody suppression is overcome by administration of C4-V3 peptides as a polyvalent immunogen

Abstract: The extreme variability of HIV-1 immunogenic regions has hampered attempts to design immunogens capable of inducing broadly reactive neutralizing anti-HIV antibody responses. We have begun to study the immune responses generated to a polyvalent mixture of HIV envelope gpl20 synthetic peptides, and to determine the ability of each component of a polyvalent immunogen to prime and boost immune responses to each immunogen component. A major concern regarding the use of a polyvalent mixture of HIV-1 immunogens is that the phenomenon of "original antigenic sin," or HIV-1 primer-induced suppression of antibody responses to a subsequent boost by a second HIV-1 variant, may occur and prevent effective anti-HIV immune responses. Using a prototypic four-valent HIV peptide envelope immunogen in BALB/c mice, we observed two types of primer-induced antibody suppression: "original antigenic sin" with primer-induced suppression of antibody responses to only the boosting immunogen, and a second, novel form of primer-induc...

AD2, a human molecule involved in the interaction of T cells with epidermal keratinocytes and thymic epithelial cells.

Abstract: Interactions between T cells and epithelial cells of the thymus are essential for normal T cell development, and interactions between T cells and skin epidermal keratinocytes occur in the context of inflammatory skin diseases and cutaneous T cell malignancies. On the basis of observations that the T cell ALL cell line, HSB, bound to IFN-gamma activated epidermal keratinocytes (41 +/- 5% of EK with three or more HSB cells bound), whereas the CTCL cell line H9 bound poorly (8 +/- 3%), we have raised mAb 13H12 that identified a 36 kDa molecule, termed AD2, that was highly expressed on HSB but not on H9 T cells. mAb 13H12 inhibited the binding of HSB T cells to IFN-gamma-treated epidermal keratinocytes (43 +/- 5% inhibition, p < 0.01), inhibited the binding of peripheral blood T cells to IFN-gamma-treated EK (62 +/- 3% inhibition, p < 0.001), and inhibited the binding of IFN-gamma-treated human thymic epithelial cells to thymocytes (39 +/- 3% inhibition, p < 0.01). Although AD2 was expressed at a low level on all T cells, AD2 was highly expressed on the CD3-CD4-CD8-, CD3-CD4low+ CD8-, and CD3-CD4+ CD8+ subsets of immature thymocytes in the thymic subcapsular and inner cortex. Taken together, these data suggest a role for the AD2 molecule in interactions of T cells with epithelial cells of skin and thymus.