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The H2-Ab gene influences the severity of experimental allergic encephalomyelitis induced by proteolipoprotein peptide 103-116

Kjellen, Peter; Jansson, Liselotte LU ; Vestberg, Mikael LU ; Andersson, Åsa LU ; Mattsson, Ragnar LU and Holmdahl, Rikard LU (2001) In Journal of Neuroimmunology 120(1-2). p.25-33
Abstract
Immunization of H2(p) and H2(q) congenic C3H mouse strains with the PLP 103-116 peptide elicited two distinct experimental allergic encephalomyelitis (EAE) disease courses. C3H.Q (H2(q)) mice developed an acute-phase disease with classical ascending paralytic signs whereas C3H.NB (H2(p)) developed a highly variable disease course with symptoms originating from CNS above the spinal chord. C3H.Q lacks functional H2-E molecules and share H2-Aalpha with C3H.NB. To examine if the differences found at positions 85, 86, 88, and 89 in the Abeta-chains account for disease susceptibility, H2(q) mice were made transgenic with the Ab(p) gene. The Ab(p)-transgenic mice on the C3H.Q background developed a more severe disease course, demonstrating the... (More)
Immunization of H2(p) and H2(q) congenic C3H mouse strains with the PLP 103-116 peptide elicited two distinct experimental allergic encephalomyelitis (EAE) disease courses. C3H.Q (H2(q)) mice developed an acute-phase disease with classical ascending paralytic signs whereas C3H.NB (H2(p)) developed a highly variable disease course with symptoms originating from CNS above the spinal chord. C3H.Q lacks functional H2-E molecules and share H2-Aalpha with C3H.NB. To examine if the differences found at positions 85, 86, 88, and 89 in the Abeta-chains account for disease susceptibility, H2(q) mice were made transgenic with the Ab(p) gene. The Ab(p)-transgenic mice on the C3H.Q background developed a more severe disease course, demonstrating the importance of class II. However, the onset was not affected and the disease showed a classical ascending paralysis similar to the C3H.Q suggesting that the observed brain symptoms were related to nonclass II genes. Inhibition studies performed on affinity purified MHC class II molecules indicated that the PLP 103-116 peptide bound to A(p) with slightly higher affinity than to A(q). Both A(q) and A(p) formed long-lived stable complexes (t(1/2)>24 h) with the PLP 103-116 peptide, but a higher amount of the peptide was loaded on to A(p) compared with A(q). An F2 gene segregation experiment, in which the low PLP 103-116 binding A(r) molecule and the high binding A(p) molecule could be compared for the influence on the disease susceptibility, indicated a role for both peptide binding affinity and non-MHC genes. Based on our results, we conclude that the H2-Ab gene controls severity of EAE but not necessarily the onset or type of disease course and that affinity of the disease-promoting peptide for the class II molecule is a critical pathogenic factor. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animal models, Multiple sclerosis, Proteolipid protein, Autoimmunity, Tolerance
in
Journal of Neuroimmunology
volume
120
issue
1-2
pages
25 - 33
publisher
Elsevier
external identifiers
  • pmid:11694316
  • scopus:0034749174
ISSN
1872-8421
DOI
10.1016/S0165-5728(01)00407-6
language
English
LU publication?
yes
id
e0e82c58-acae-4615-8e50-c5631efd23bf (old id 1120534)
date added to LUP
2008-07-01 14:07:40
date last changed
2018-01-07 05:39:54
@article{e0e82c58-acae-4615-8e50-c5631efd23bf,
  abstract     = {Immunization of H2(p) and H2(q) congenic C3H mouse strains with the PLP 103-116 peptide elicited two distinct experimental allergic encephalomyelitis (EAE) disease courses. C3H.Q (H2(q)) mice developed an acute-phase disease with classical ascending paralytic signs whereas C3H.NB (H2(p)) developed a highly variable disease course with symptoms originating from CNS above the spinal chord. C3H.Q lacks functional H2-E molecules and share H2-Aalpha with C3H.NB. To examine if the differences found at positions 85, 86, 88, and 89 in the Abeta-chains account for disease susceptibility, H2(q) mice were made transgenic with the Ab(p) gene. The Ab(p)-transgenic mice on the C3H.Q background developed a more severe disease course, demonstrating the importance of class II. However, the onset was not affected and the disease showed a classical ascending paralysis similar to the C3H.Q suggesting that the observed brain symptoms were related to nonclass II genes. Inhibition studies performed on affinity purified MHC class II molecules indicated that the PLP 103-116 peptide bound to A(p) with slightly higher affinity than to A(q). Both A(q) and A(p) formed long-lived stable complexes (t(1/2)>24 h) with the PLP 103-116 peptide, but a higher amount of the peptide was loaded on to A(p) compared with A(q). An F2 gene segregation experiment, in which the low PLP 103-116 binding A(r) molecule and the high binding A(p) molecule could be compared for the influence on the disease susceptibility, indicated a role for both peptide binding affinity and non-MHC genes. Based on our results, we conclude that the H2-Ab gene controls severity of EAE but not necessarily the onset or type of disease course and that affinity of the disease-promoting peptide for the class II molecule is a critical pathogenic factor.},
  author       = {Kjellen, Peter and Jansson, Liselotte and Vestberg, Mikael and Andersson, Åsa and Mattsson, Ragnar and Holmdahl, Rikard},
  issn         = {1872-8421},
  keyword      = {Animal models,Multiple sclerosis,Proteolipid protein,Autoimmunity,Tolerance},
  language     = {eng},
  number       = {1-2},
  pages        = {25--33},
  publisher    = {Elsevier},
  series       = {Journal of Neuroimmunology},
  title        = {The H2-Ab gene influences the severity of experimental allergic encephalomyelitis induced by proteolipoprotein peptide 103-116},
  url          = {http://dx.doi.org/10.1016/S0165-5728(01)00407-6},
  volume       = {120},
  year         = {2001},
}