By Edgar Haber
Issues coated comprise: 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 gains * 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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Measuring epitope densities of naturally processed (endogenous) peptides on the cells that produce them requires a different approach. , 1990a). , 1993). , 1995). , a reasonable next step will be to measure the abundance of these peptides in order to find out whether epitope densities commonly limit T-cell responses (Tsomides, 1995). E. TCR-PepMHC Engagement: An Afinity Model The intensity of the T-cell response has been widely assumed to be determined, in large measure, by TCR affinity for pepMHC complexes and the number of these complexes on target cells (epitope density).
B. C D 4 a n d C D 8 As noted in Section 11, the mutually exclusive expression of cell surface glycoproteins CD4 and CD8 on mature T cells distinguishes between the two major T-cell lineages. , 1993). CD4 is a singlechain transmembrane glycoprotein, while CD8, which consists of two membrane-associated polypeptides, can be either an aa homodimer or an a/3 heterodimer; functional distinctions between them are not yet clear (see Weiss and Littman, 1994). In humans and mice, -60% of peripheral ap TCR+ cells are CD4+ cells and the rest are CD8+.
Leuscher et al. (1995), however, have succeeded in showing with intact T cells and a photoaffinity-labeled soluble pepMHC-I complex that CD8 can modulate the TCR-pepMHC interaction. Different monoclonal antibodies to CD8a and CD8a chains appear to have different effects on the CD8-MHC-I interaction; while most antLCD8 antibodies are inhibitory, some enhanced CD8-MHC binding, suggesting that small conformational changes in the CD8 protein might influence its interaction with MHC. It is possible that the extent of interaction of CD4 and CD8 with MHC proteins may depend on the particular TCR and pepMHC complexes involved.
Antibodies and T-Cell Receptors, by Edgar Haber