By Edgar Haber

Subject matters coated contain: X-ray crystallography of ligands. Catalytic antibodies. Nature of the antigen. Antibody binding websites. Maturation of the immune reaction. Computational biochemistry of antibodies and T-cell receptors. Antigen-specific T-cell receptors and their reactions. Key beneficial properties * X-Ray Crystallography of Ligands * Catalytic Antibodies * Nature of the Antigen * Antibody Binding websites * Maturtion of the Immune reaction * Computational Biochemistry of Antibodies and * T-Cell Receptors * Antigen-Specific T-Cell Receptors and Their Reactions

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5 x lo1' cpm per mole of monoiodinated peptide, the same as the specific activity of carrier-free L251 (Tsomides and Eisen, 1993b)l. The epitope densities found by this direct approach and those calculated by Eq. (1)agreed to within a factor of 2 or 3 . When the same high specific activity peptide (1251~-QL9-Y5) was added to target cells at a concentration that resulted in half-maximal cytotoxicity (SD50-5 pM), an average of only three peptide molecules were bound to Ld per target cell. A single 32 HERMAN N.

R. (4) (4) (4) 50d ' Peptide sequences given in Table 111. , surface plasmon resonance. ' ( I ) Sykulev et al. (1994b); ( 2 )Sykulev et al. (1994a); ( 3 )Corr et al. (1994); (4) Matsui et al. (1994). MHC reaction and L is unbound peptide concentration; under physiological conditions @ + I ) (L) << (k-1) and t is thus effectively determined by l/k-1. MHC reaction modeled as either a classic bimolecular reaction (upper line) or a two-step reaction (fast and slow, lower line); in the latter case only the fast component of k+ 1 and the slow component of ti12 are given.

1991). , 1990). , peptide-free or with weakly bound peptides derived perhaps from protein ANTIGEN-SPECIFIC T-CELL RECEPTORS 31 signal sequences), and then they undergo rapid denaturation (at 37°C) unless stabilized by the binding of synthetic extracellular peptides. By raising the extracellular concentration of peptide, the cell surface epitope density is increased, resulting in greater target cell lysis by CTL. , 1991) is a useful indicator (though not in itself a measure) of the density of pepMHC complexes needed to elicit CTL-mediated lysis.

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