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B P Babbitt

Publications and source records attributed to B P Babbitt.

5 recordsLinked to original sources
PubMed1986

Antigenic competition at the level of peptide-Ia binding.

We examined the direct binding of a hen egg white lysozyme peptide, HEL(46-61), to membrane I-Ak (protein encoded in the A locus of the I region) molecules in the presence of detergent. A number of synthetic peptide derivatives, which did not stimulate our T-cell reactive hybridomas, competed for the binding of HEL(46-61) to I-Ak and also inhibited the functional presentation of HEL(46-61). Inhibitors included a peptide lacking a tyrosine at position 53 and a peptide corresponding to the autologous lysozyme peptide. Presentation was examined with cells or with supported planar phospholipid membranes bearing only I-Ak and HEL(46-61). Other peptides that did not compete for the binding did not inhibit functional presentation. We concluded that the binding of an immunogenic peptide to I-A is critical for presentation, that the I-A molecule does not discriminate between autologous and foreign related determinants but does recognize structurally different peptides. Our evidence suggests that our immunogenic peptide bears noncontiguous amino acids critical for contact I-A binding interspersed with amino acids critical for interaction with T cells.

Amino Acid Sequence↗
PubMed1985

Effects of valency on thermodynamic parameters of specific membrane interactions.

We have measured the equilibrium binding of dioleoylphosphatidylcholine vesicles (800-A diameter) containing various densities of incorporated palmitoyl-alpha-bungarotoxin (PBGT) to acetylcholine receptor (AchR) enriched microsac membranes. We have previously shown that these PBGT vesicles bind specifically to the microsacs mediated by direct interactions with the AchRs [Grant, S. W., Babbitt, B. P., West, L. K., & Huang, L. (1982) Biochemistry 21, 1274-1279]. The percent binding of liposomal lipid and associated PBGT to excess AchR sites, as well as the inhibition of binding by pretreatment of microsacs with excess alpha-bungarotoxin (alpha BGT), was strongly dependent upon the protein/lipid molar ratio of the vesicles. In addition, there existed a threshold level of approximately six PBGT molecules per vesicle at which the binding increased dramatically. The apparent association constant, KAapp, for lipid vesicle-microsac membrane binding increased approximately 4800-fold (from 3.95 X 10(4) to 1.90 X 10(8) M-1) due to an increase of 20-fold in the vesicle-associated PBGT surface density. Direct competition for binding to microsac membranes between vesicles with different PBGT/lipid molar ratios indicated that multivalent binders could easily replace binders of lower valency when receptor sites were limited. Measurement of the temperature dependence of the KAapp indicated that weak (low valency) and medium strength (intermediate valency) PBGT vesicle binders bound to microsacs in a fashion similar to the binding of alpha BGT and PBGT to detergent-solubilized AchRs. Strong PBGT vesicle binders (high valency) appear to bind by a somewhat different mechanism. All results are discussed in terms of the effects of ligand (PBGT) valency on the binding strength of vesicles to microsac membranes.

Bungarotoxins↗
PubMedDate not supplied

Binding of immunogenic peptides to Ia histocompatibility molecules.

Most cellular interactions essential for the development of an immune response involve the membrane glycoproteins encoded in the major histocompatibility gene complex. The products of the I region, the class II histocompatibility molecules (Ia molecules), are essential for accessory cells such as macrophages to present polypeptide antigens to helper T cells. This interaction, antigen presentation, is needed for T-cell recognition of the antigen and its consequent activation. How the Ia molecules regulate the immune response during antigen presentation is not known, although it is commonly thought to result from their association with the presented antigen. Recent studies, including the elucidation of the structure of the T-cell receptor, favour recognition of a single structure, an antigen-Ia complex. Here we report attempts to determine whether purified Ia glycoproteins have an affinity for polypeptide antigens presented by intact cells in an Ia-restricted manner. We first identified the epitope of a peptide antigen involved in presentation. Several laboratories have shown that globular proteins are altered (processed) in intracellular vesicles of the antigen-presenting cell before antigen presentation. A major component of the T-cell response is directed toward determinants found in the unfolded or denatured molecule, and our laboratory has shown that the determinant of the hen-egg lysozyme protein (HEL), presented in H-2k mice to T cells, is a sequence of only 10 amino acids. This portion resides in an area of the native molecule partially buried inside the molecule, in a beta-sheet conformation. To be presented, intact or native HEL must first be processed in acidic intracellular vesicles. Having isolated the peptide responsible for T-cell recognition of HEL, we sought a physical association of this peptide with purified, detergent-solubilized I-Ak molecules from B-hybridoma cells. We have found such an association, which may explain the role of the Ia glycoproteins in cellular interactions.

Animals↗