TY  - JOUR
N1  - Copyright of this article belongs to Elsevier Science.
ID  - open2438
UR  - https://www.sciencedirect.com/science/article/pii/S0264410X13010104?via%3Dihub
IS  - 41
A1  - Ghosh, Moumita
A1  - Solanki, Ashish K
A1  - Roy, Koushik
A1  - Dhoke, Reema R
A1  - Ashish, .
A1  - Roy, Syamal
Y1  - 2013/09/23/
N2  - 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 [?R(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 ?R(12-26) in N-KMP-11 and C-KMP-11 was established by western blot analysis with antibody to ?R(12-26) peptide. N-KMP-11 but not C-KMP-11 could stimulate the anti ?R(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-?R(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.
PB  - Elsevier Science
JF  - Vaccine
VL  - 31
KW  - 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; ?R((12?26)); ?R((12?26)) engineered at the C termini of KMP-11; ?R((12?26)) engineered at the N termini of KMP-11
SN  - 1873-2518
TI  - Carrier protein influences immunodominance of a known epitope: implication in peptide vaccine design.
SP  - 4682
EP  - 8
ER  -