Cargando…

The relationship between predicted peptide–MHC class II affinity and T-cell activation in a HLA-DRβ1*0401 transgenic mouse model

The HLA-DRB1*0401 MHC class II molecule (DR4) is genetically associated with rheumatoid arthritis. It has been proposed that this MHC class II molecule participates in disease pathogenesis by presenting arthritogenic endogenous or exogenous peptides to CD4(+) T cells, leading to their activation and...

Descripción completa

Detalles Bibliográficos
Autores principales: Hill, Jonathan A, Wang, Dequn, Jevnikar, Anthony M, Cairns, Ewa, Bell, David A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC154425/
https://www.ncbi.nlm.nih.gov/pubmed/12716452
http://dx.doi.org/10.1186/ar605
_version_ 1782120747930484736
author Hill, Jonathan A
Wang, Dequn
Jevnikar, Anthony M
Cairns, Ewa
Bell, David A
author_facet Hill, Jonathan A
Wang, Dequn
Jevnikar, Anthony M
Cairns, Ewa
Bell, David A
author_sort Hill, Jonathan A
collection PubMed
description The HLA-DRB1*0401 MHC class II molecule (DR4) is genetically associated with rheumatoid arthritis. It has been proposed that this MHC class II molecule participates in disease pathogenesis by presenting arthritogenic endogenous or exogenous peptides to CD4(+) T cells, leading to their activation and resulting in an inflammatory response within the synovium. In order to better understand DR4 restricted T cell activation, we analyzed the candidate arthritogenic antigens type II collagen, human aggrecan, and the hepatitis B surface antigen for T-cell epitopes using a predictive model for determining peptide–DR4 affinity. We also applied this model to determine whether cross-reactive T-cell epitopes can be predicted based on known MHC–peptide–TCR interactions. Using the HLA-DR4-IE transgenic mouse, we showed that both T-cell proliferation and Th1 cytokine production (IFN-γ) correlate with the predicted affinity of a peptide for DR4. In addition, we provide evidence that TCR recognition of a peptide–DR4 complex is highly specific in that similar antigenic peptide sequences, containing identical amino acids at TCR contact positions, do not activate the same population of T cells.
format Text
id pubmed-154425
institution National Center for Biotechnology Information
language English
publishDate 2003
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-1544252003-05-07 The relationship between predicted peptide–MHC class II affinity and T-cell activation in a HLA-DRβ1*0401 transgenic mouse model Hill, Jonathan A Wang, Dequn Jevnikar, Anthony M Cairns, Ewa Bell, David A Arthritis Res Ther Research Article The HLA-DRB1*0401 MHC class II molecule (DR4) is genetically associated with rheumatoid arthritis. It has been proposed that this MHC class II molecule participates in disease pathogenesis by presenting arthritogenic endogenous or exogenous peptides to CD4(+) T cells, leading to their activation and resulting in an inflammatory response within the synovium. In order to better understand DR4 restricted T cell activation, we analyzed the candidate arthritogenic antigens type II collagen, human aggrecan, and the hepatitis B surface antigen for T-cell epitopes using a predictive model for determining peptide–DR4 affinity. We also applied this model to determine whether cross-reactive T-cell epitopes can be predicted based on known MHC–peptide–TCR interactions. Using the HLA-DR4-IE transgenic mouse, we showed that both T-cell proliferation and Th1 cytokine production (IFN-γ) correlate with the predicted affinity of a peptide for DR4. In addition, we provide evidence that TCR recognition of a peptide–DR4 complex is highly specific in that similar antigenic peptide sequences, containing identical amino acids at TCR contact positions, do not activate the same population of T cells. BioMed Central 2003 2002-11-04 /pmc/articles/PMC154425/ /pubmed/12716452 http://dx.doi.org/10.1186/ar605 Text en Copyright © 2003 Hill et al., licensee BioMed Central Ltd. This is an Open Access article: Media for any non-commercial purpose, provided this notice is presented along with the articles original URL.
spellingShingle Research Article
Hill, Jonathan A
Wang, Dequn
Jevnikar, Anthony M
Cairns, Ewa
Bell, David A
The relationship between predicted peptide–MHC class II affinity and T-cell activation in a HLA-DRβ1*0401 transgenic mouse model
title The relationship between predicted peptide–MHC class II affinity and T-cell activation in a HLA-DRβ1*0401 transgenic mouse model
title_full The relationship between predicted peptide–MHC class II affinity and T-cell activation in a HLA-DRβ1*0401 transgenic mouse model
title_fullStr The relationship between predicted peptide–MHC class II affinity and T-cell activation in a HLA-DRβ1*0401 transgenic mouse model
title_full_unstemmed The relationship between predicted peptide–MHC class II affinity and T-cell activation in a HLA-DRβ1*0401 transgenic mouse model
title_short The relationship between predicted peptide–MHC class II affinity and T-cell activation in a HLA-DRβ1*0401 transgenic mouse model
title_sort relationship between predicted peptide–mhc class ii affinity and t-cell activation in a hla-drβ1*0401 transgenic mouse model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC154425/
https://www.ncbi.nlm.nih.gov/pubmed/12716452
http://dx.doi.org/10.1186/ar605
work_keys_str_mv AT hilljonathana therelationshipbetweenpredictedpeptidemhcclassiiaffinityandtcellactivationinahladrb10401transgenicmousemodel
AT wangdequn therelationshipbetweenpredictedpeptidemhcclassiiaffinityandtcellactivationinahladrb10401transgenicmousemodel
AT jevnikaranthonym therelationshipbetweenpredictedpeptidemhcclassiiaffinityandtcellactivationinahladrb10401transgenicmousemodel
AT cairnsewa therelationshipbetweenpredictedpeptidemhcclassiiaffinityandtcellactivationinahladrb10401transgenicmousemodel
AT belldavida therelationshipbetweenpredictedpeptidemhcclassiiaffinityandtcellactivationinahladrb10401transgenicmousemodel
AT hilljonathana relationshipbetweenpredictedpeptidemhcclassiiaffinityandtcellactivationinahladrb10401transgenicmousemodel
AT wangdequn relationshipbetweenpredictedpeptidemhcclassiiaffinityandtcellactivationinahladrb10401transgenicmousemodel
AT jevnikaranthonym relationshipbetweenpredictedpeptidemhcclassiiaffinityandtcellactivationinahladrb10401transgenicmousemodel
AT cairnsewa relationshipbetweenpredictedpeptidemhcclassiiaffinityandtcellactivationinahladrb10401transgenicmousemodel
AT belldavida relationshipbetweenpredictedpeptidemhcclassiiaffinityandtcellactivationinahladrb10401transgenicmousemodel