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 good points * 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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Extra info for Antibodies and T-Cell Receptors,
1994) measured their interaction by surface plasmon resonance. In this procedure, pepMHC complexes flow over 27 ANTIGEN-SPECIFIC T-CELL RECEPTORS TABLE IV Kinetic Constantsfor Binding of PeptideeMHC Complexes to TCR Ligand (peptideoMHC)' (M-' sec-') tl/Z(off) (sec) QL9*Ld QLS~L~ p 2 ~ a . 3 x lo4 3 . r. r. r. r. 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.
Since it was suggested that many serial engagements enhance T-cell responses, Valitutti et al. (1995) predicted that high TCR-pepMHC dissociation rates, which are generally associated with low-affinity reactions, would promote T-cell responses. , 1994a,b). F. SpeciJicity,Degeneracy, and Molecular Mimicry It seems to be widely believed that high levels of specificity in immune reactions are manifestations of high-affinity interactions. However, measurements of TCR affinities have shown that exquisite specificity can be manifested by very low-affinity reactions.
5). As shown in Fig. 5 and predicted by Eq. (3), over a wide range of affinity values ( Clo4 to about lo6 M-'), the log epitope density was a linear function of the log TCR affinity with a slope of -1. The fit suggests that in a T cell-target cell conjugate the extent of ligation of the T cell's TCR molecules by pepMHC complexes on the target cell can be described by a relationship in the form of the law of mass action (Fig. 5). The validity of this model should become evident when its predictive ability is put to the test: Since the product of epitope density and TCR affinity is constant (over the linear range shown in Fig.