The ring-infected erythrocyte surface antigen (RESA) is a dense-granule protein which
June 9, 2017
The ring-infected erythrocyte surface antigen (RESA) is a dense-granule protein which binds to the cytoskeletal structure of the erythrocyte after parasite invasion. Nucleotide sequencing of the random oligonucleotide insert revealed a common predominant motif: (S/T)AVDD. Several other clones experienced related but degenerate motifs. Thus, a monoclonal antibody against a malarial antigen can select common mimotopes from different random peptide libraries. We envisage many uses for this technology in malaria research. Libraries of random peptides expressed on the surface of phage provide vast pools of diverse molecular structures from which peptides with binding affinities toward desired molecules can be selected (39). Screening such libraries has emerged as a powerful tool in the identification of small peptides that mimic structural and functional features of larger molecules, e.g., identification of epitopes or mimotopes (a peptide that mimics an epitope but has a different main amino acid sequence) on antigens (28). In addition, small peptides with affinity for molecules involved in Carfilzomib biological interactions (such as receptors) can be isolated and assessed as possible functional modulators. We have used phage peptide technology Rabbit Polyclonal to OR2AG1/2. to obtain mimotopes for an important malarial antigen, the ring-infected erythrocyte surface antigen (RESA). RESA is usually a protein produced by the most pathogenic of the human malaria parasites, Carfilzomib molecular chaperone, DnaJ (11). This region may Carfilzomib be responsible for the proposed chaperone-like activity of RESA (17, 21). These functional regions of the RESA molecule are flanked by two regions of repetitive acidic amino acid sequence, the so-called 5 and 3 repeat regions. These acidic repeats represent immunodominant epitopes (19) and are recognized by sera of people who are naturally exposed to malaria (32). Indeed, a number of Carfilzomib studies examining malaria endemicity and other seroepidemiological parameters have relied on synthetic peptides corresponding to the linear repeat sequences of RESA (29, 33, 34). The Carfilzomib function of the repetitive sequences of RESA is not obvious. Many malaria antigens have extensive regions of their amino acid sequence composed of repetitive sequences, some of which are probably the targets of the protective immune response (6). Other repeats, including some that are recognized as dominant epitopes by the host immune system, may function as molecular smoke cigarettes screens, decreasing the power from the web host to mount a highly effective immune system response (4, 26). Although RESA isn’t exposed at the top of contaminated erythrocyte (3) and isn’t essential for development in vitro (12), proof from several research provides indicated that antibodies against RESA can inhibit the invasion of merozoites in to the web host erythrocyte (1, 38). Furthermore, immunization of monkeys with recombinant RESA presents some security from malaria problem (14). It has led to the theory that antibodies towards the RESA molecule might cross-react with another malarial proteins that plays a significant function in invasion or advancement of the intraerythrocytic parasite. A diacidic theme found within both 5 and 3 do it again parts of RESA can be discovered within the do it again parts of the falciparum interspersed do it again antigen, the FC27 S-antigen, Pf332, Pf11.1, and erythrocyte music group 3 (6, 25, 38). A individual monoclonal antibody (MAb 33G2) provides been proven to cross-react with Pf322 and RESA (27). Certainly, anti-Pf322 antibodies that cross-react using the acidic do it again regions on the C terminus of RESA had been discovered to inhibit the development of parasites even though the parasite stress did not exhibit RESA (38). These research claim that antibodies spotting the repeat parts of RESA could be essential antimalarial agents because of their promiscuous binding activity also to the current presence of diacidic motifs in lots of parasite antigens. In this scholarly study, we utilized phage peptide technology to acquire information regarding the binding specificity of the anti-RESA monoclonal antibody, MAb 18/2. MAb 18/2 grew up against a C-terminal.