Peptide antigens

Other types of branched peptide dendrimers, known as multiple antigen peptides (MAPs), have been synthesized to mimic proteins for applications, for instance as synthetic vaccines, serodiagnostics, peptide inhibitors and intracellular delivery vehicles. Since this concept has been recently described in detail elsewhere [11], only the conceptual framework will be briefly presented here. Tam and coworkers have developed a dendritic core based on lysine units for the construction of MAPs [12-15] (Fig. 3). Carrying antigens at their periphery these MAPs have been designed to increase antigenicity and immunogenicity of peptides. 

Recently, Tam et al. extended their orthogonal ligation concept, using the thermodynamically driven formation of a thiazolidine ring for the synthesis of dendritic compounds that carry cyclic peptides at the surface, which were designated multiple cyclic antigen peptides (McAPs) [18,19]. 

Price, M.R., Sekowski, M., Hooi, D.S.W., Durrant, L.G., Hudecz, F., and Tendler, S.J.B. (1993) Measurement of antibody binding to antigenic peptides conjugated in situ to albumin-coated microti-tre plates./. Immunol. Meth. 159, 277-281. 

Tam, J.P. (1988) Synthetic peptide vaccine design Synthesis and properties of a high-density multiple antigenic peptide system. Proc. Natl. Acad. Sci. USA 85, 5409-5413. 

T., and Rock, K. L. The importance of the proteasome and subsequent proteolytic steps in the generation of antigenic peptides. Mol Immunol 2002, 39 147-64. 

O Sullivan D, et al. On the interaction of promiscuous antigenic peptides with different DR alleles. Identification of common structural motifs. J Immunol 1991 147 2663. 

Proteasomes are large cytoplasmic complexes that have multiple protease activities capable of sequentially digesting damaged proteins. Many proteins are marked for digestion by addition of several molecules of ubiquitin (polyubiquination). Proteasomes may also play a role in producing antigenic peptides for presentation by class IMHC molecules. 

Several antigenic peptides that are naturally processed and presented by A2.1 and corresponding to human wild-type (wt) p53, hdm2, and CD19 sequences have been identified in the laboratory. Tg mice-derived CTL lines specific for the identified wt p53 and hdm2 peptide epitopes were of sufficiently high... 

To initiate a T-cell immune response, antigen presenting cells have to display antigenic peptides com-plexed with the major histocompatibility complex (MHC) on their cell surface. The T-cell receptor of CDS cells is specific for the peptide-MHC class I complex while the CD4 cell receptor binds the peptide-MHC class II complex. This binding of the peptide-MHC II complex stimulates CD4 cell proliferation and subsequent lymphokine release. This CD4 cell response can initiate a delayed hypersensitivity reaction. However CD4 activation and the production of various lymphokines is also needed for the generation of cytotoxic T-cells and for the differentiation of plasma cells from B-lymphocytes and the antibody response by these plasma cells. For their role in also the humoral immune response CD4 cells are called T-helper cells. 

Two types of expression systems based on plant RNA viruses have been developed for production of immunogenic peptides and proteins in plants epitope presentation systems (short antigenic peptides fused to the CP that are displayed on the surface of assembled viral particles) and polypeptide expression systems (these systems express the whole unfused recombinant protein that accumulates within the plant). 

FIGURE 4.2 Schematic diagram of RNA virus expression vectors, (a) TMV as an epitope presentation system, and (b) a polypeptide presentation system. Dark diamonds represent foreign antigen/peptide. 

Charterji, A., Bnms, L.L., Taylor, S.S. et al. (2002). Cowpea mosaic virus from the presentation of antigenic peptides to the display of active biomaterials. Intervirology 45 362-370. 

Fig. 11.1. Principle of an immunological synapse. Possibilities for communication between B and T cells during an immune response. Antigenic peptides are presented by the MHC complex class II at the surface of the B cell. The antigens are recognized and bound by T cell receptors of the T cell. The T cell receptor is activated and sets a signal chain in motion that leads to activation of the expression of cytokines, such as IL-2. The cytokine is secreted, and binds and activates a cytokine receptor on the B cell. TNFa is shown as another example of a ligand-receptor system. TNFa communicates, as a membrane-bound ligand, with a corresponding receptor on the surface of the B cell. The interactions shown take place in a narrow spatial region between B and T cells, which is why this system is referred to as an immunological synapse. TNF tumor necrosis factor MHC major histocompatibility complex IL-2 interleukin 2.

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