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Subtle sequence differences in a turnour-associated peptide epitope translate into major changes in antigenicity

Persson, Jonas LU ; Lantto, Johan LU ; Drakenberg, Torbjörn LU and Ohlin, Mats LU (2005) In Molecular Immunology 42(11). p.1321-1330
Abstract
Antigenicity, the ability to bind to members of repertoire of diverse immune receptors, is a concept that is poorly characterised with respect to its defining parameters. To learn more about its makeup, we have investigated the ability of two peptides with highly related sequences, derived from the tumour-associated antigen mucin-1, to recruit in vitro members from a large naive repertoire of synthetic human antibody fragments. One of the peptides represents the epitope that is immunodominant in mice. We now demonstrate that the other peptide, which differs from the first only by a very conservative aspartate-threonine to glutamate-serine change, is much less antigenic than the first peptide. This is so despite the fact that there is no... (More)
Antigenicity, the ability to bind to members of repertoire of diverse immune receptors, is a concept that is poorly characterised with respect to its defining parameters. To learn more about its makeup, we have investigated the ability of two peptides with highly related sequences, derived from the tumour-associated antigen mucin-1, to recruit in vitro members from a large naive repertoire of synthetic human antibody fragments. One of the peptides represents the epitope that is immunodominant in mice. We now demonstrate that the other peptide, which differs from the first only by a very conservative aspartate-threonine to glutamate-serine change, is much less antigenic than the first peptide. This is so despite the fact that there is no observable difference in the tendency of the two peptides to adopt a structure in solution. Furthermore, the peptides differ in their immunodominant parts and the less antigenic peptide selects for antibody fragments targeting residues outside of the epitope considered to be immunodominant in mice. We conclude that subtle sequence changes greatly, affect antigenicity and immunodominance of epitopes in this important tumour-associated antigen. (c) 2005 Elsevier Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Immunology
volume
42
issue
11
pages
1321 - 1330
publisher
Pergamon
external identifiers
  • pmid:15950728
  • wos:000230336400007
  • scopus:20444408755
ISSN
1872-9142
DOI
10.1016/j.molimm.2004.12.010
language
English
LU publication?
yes
id
ef5fc94a-09af-4484-be79-cc648a05f568 (old id 152130)
date added to LUP
2007-06-29 14:16:27
date last changed
2017-01-01 07:08:36
@article{ef5fc94a-09af-4484-be79-cc648a05f568,
  abstract     = {Antigenicity, the ability to bind to members of repertoire of diverse immune receptors, is a concept that is poorly characterised with respect to its defining parameters. To learn more about its makeup, we have investigated the ability of two peptides with highly related sequences, derived from the tumour-associated antigen mucin-1, to recruit in vitro members from a large naive repertoire of synthetic human antibody fragments. One of the peptides represents the epitope that is immunodominant in mice. We now demonstrate that the other peptide, which differs from the first only by a very conservative aspartate-threonine to glutamate-serine change, is much less antigenic than the first peptide. This is so despite the fact that there is no observable difference in the tendency of the two peptides to adopt a structure in solution. Furthermore, the peptides differ in their immunodominant parts and the less antigenic peptide selects for antibody fragments targeting residues outside of the epitope considered to be immunodominant in mice. We conclude that subtle sequence changes greatly, affect antigenicity and immunodominance of epitopes in this important tumour-associated antigen. (c) 2005 Elsevier Ltd. All rights reserved.},
  author       = {Persson, Jonas and Lantto, Johan and Drakenberg, Torbjörn and Ohlin, Mats},
  issn         = {1872-9142},
  language     = {eng},
  number       = {11},
  pages        = {1321--1330},
  publisher    = {Pergamon},
  series       = {Molecular Immunology},
  title        = {Subtle sequence differences in a turnour-associated peptide epitope translate into major changes in antigenicity},
  url          = {http://dx.doi.org/10.1016/j.molimm.2004.12.010},
  volume       = {42},
  year         = {2005},
}