Table 2.
Usage of linker sequences in different studies with the aim to ensure the correct processing/directing of peptides in multiepitope vaccines
| Linker Sequence |
Description | Reference |
|---|---|---|
| Ubiquitin | The introduction of the coding sequence of the ubiquitin gene at one extremity of the vaccine construction aims to favor the peptide degradation by proteasomes during the epitope-specific CTL response | 56–58 |
| GPGPG | The introduction of this spacer between MHC-II binding epitopes in multiepitope vaccine construction promotes the disruption of junctional epitopes in these vaccines, restoring immunogenicity against the target epitopes during helper response | 55,59–61 |
| EAAAK | It consists of a helical linker to control the distance and reduce the interference between the domains of functional proteins with other protein regions in the vaccine construction. Thus, it is ideally incorporated into N and C-terminal of B cell conformational epitopes | 59,60,62 |
| ALL and SSL | These linkers are expected to direct the cleavage to the C-terminus of the preceding peptide and to the N-terminus of the next peptide | 63 |
| RKSYL and RKSY | Similar to the previous sequence, these motifs are expected to direct the cleavage to the C-terminus of the proceeding peptide, but enable a more flexible cleavage at the N-terminus of the next peptide with multiple potential cleavage sites, optimizing binding to TAP transporter | 63 |
| KFLRQY; ADRIW; ADKQW; ADRQW; ADNQY; AKRW; ADNIW. | The initial amino acids of each of these flanking sequences aim to optimize the processing and release of epitopes by the proteasome, and, after cleavage, the following amino acids provide binding sites to TAP transporter | 57 |
| ARY | This sequence is a high-affinity motif for TAP recognition based on the preferences of human TAP for flanking of epitopes in the polyepitope construct | 64 |
| R/K-R/K | The introduction of a dibasic motif flanking MHC-II binding epitopes in a polyepitope construct enhances its processing, since these motifs represent cleavage sites for lysosomal cathepsins B and L, thus optimizing helper response activation | 56,65 |
| RKRSHAGYQTI; YQTI | This sequence represents the C-terminal tyrosine-based motif of LAMP-1 (lysosome-associated membrane protein-1) glycoprotein and its function is to direct the immunogen from the secretory pathway to lysosomes for degradation, where the peptide fragments bind to MHC class II molecules. Thus, this strategy allows the redirecting of gene vaccines activation route for the activation of the helper response as well | 56,66 |