Ghosh, Moumita and Solanki, Ashish K and Roy, Koushik and Dhoke, Reema R and Ashish, . and Roy, Syamal (2013) Carrier protein influences immunodominance of a known epitope: implication in peptide vaccine design. Vaccine, 31 (41). pp. 4682-8. ISSN 1873-2518
Full text not available from this repository. (Request a copy)Abstract
We investigated how the processing of a given antigen by antigen presenting cells (APC) is dictated by the conformation of the antigen and how this governs the immunodominance hierarchy. To address the question, a known immunodominant sequence of bacteriophage lambda repressor N-terminal sequence 12-26 [λR(12-26)] was engineered at the N and C termini of a heterologous leishmanial protein, Kinetoplastid membrane protein-11 (KMP-11); the resulting proteins were defined as N-KMP-11 and C-KMP-11 respectively. The presence of λR(12-26) in N-KMP-11 and C-KMP-11 was established by western blot analysis with antibody to λR(12-26) peptide. N-KMP-11 but not C-KMP-11 could stimulate the anti λR(12-26) T-cell clonal population very efficiently in the presence of APCs. Priming of BALB/c mice with N-KMP-11 or C-KMP-11 generated similar levels of anti-KMP-11 IgG, but anti-λR(12-26) specific IgG was observed only upon priming with N-KMP-11. Interestingly, uptake of both N-KMP-11 and C-KMP-11 by APCs was similar but catabolism of N-KMP-11 but not C-KMP-11 was biphasic and fast at the initial time point. Kratky plots of small angle X-ray scattering showed that while N-KMP-11 adopts flexible Gaussian type of topology, C-KMP-11 prefers Globular nature. To show that KMP-11 is not unique as a carrier protein, an epitope (SPITBTNLBTMBK) of Plasmodium yoelii (PY) apical membrane protein 1[AMA-1 (136-148)], is placed at the C and N terminals of a dominant T-cell epitope of ovalbumin protein OVA(323-339) and the resulting peptides are defined as PY-OVA and OVA-PY respectively. Interestingly, only OVA-PY could stimulate anti-OVA T-cells and produce IgG response upon priming of BALB/c mice with it. Thus for rational design of peptide vaccine it is important to place the dominant epitope appropriately in the context of the carrier protein.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to Elsevier Science. |
| Uncontrolled Keywords: | AMA-1; APC; Antigen processing; Antigen structure; C-KMP-11; Endoproteolysis; Immunodominance; KMP-11; N-KMP-11; OVA((323–339)); PY; an epitope of AMA-1((136–148)); antigen presenting cell; dominant T-cell epitope of ovalbumin protein; immunodominant sequence of bacteriophage lambda repressor N-terminal sequence; kinetoplastid membrane protein-11; plasmodium yoelii apical membrane protein 1; λR((12–26)); λR((12–26)) engineered at the C termini of KMP-11; λR((12–26)) engineered at the N termini of KMP-11 |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 05 Sep 2019 13:47 |
| Last Modified: | 05 Sep 2019 13:47 |
| URI: | http://crdd.osdd.net/open/id/eprint/2438 |
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