Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis.
Rheumatoid arthritis (RA) is associated with certain MHC class II alleles and is characterized by a chronic autoimmune response in the joints. Using transgenic mice expressing human DR4 (DRB1*0401) and human CD4, but lacking endogenous MHC class II, we show that posttranslational glycosylation of ty...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2002
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| _version_ | 1797100985391251456 |
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| author | Bäcklund, J Carlsen, S Höger, T Holm, B Fugger, L Kihlberg, J Burkhardt, H Holmdahl, R |
| author_facet | Bäcklund, J Carlsen, S Höger, T Holm, B Fugger, L Kihlberg, J Burkhardt, H Holmdahl, R |
| author_sort | Bäcklund, J |
| collection | OXFORD |
| description | Rheumatoid arthritis (RA) is associated with certain MHC class II alleles and is characterized by a chronic autoimmune response in the joints. Using transgenic mice expressing human DR4 (DRB1*0401) and human CD4, but lacking endogenous MHC class II, we show that posttranslational glycosylation of type II collagen (CII) influences the level of T cell tolerance to this candidate cartilage-specific autoantigen. In such mice, the expression of human CII resulted in a tolerized murine T cell response to human CII. However, tolerance induction remained incomplete, preferentially deleting responses to the nonmodified CII 263-270 epitope, whereas T cell recognition of a glycosylated variant of this epitope was affected to a lesser degree. A similar dominance of T cell responses to CII-glycopeptides was recorded in a cohort of severely affected RA-patients (n = 14). Thus, RA T cells predominantly recognize the immunodominant CII peptide in its glycosylated form and may explain why previously it has been difficult to detect T cell responses to CII in RA patients. |
| first_indexed | 2024-03-07T05:45:27Z |
| format | Journal article |
| id | oxford-uuid:e7128996-91f8-4744-97ce-7f6c0a34ebc2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:45:27Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:e7128996-91f8-4744-97ce-7f6c0a34ebc22022-03-27T10:35:45ZPredominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e7128996-91f8-4744-97ce-7f6c0a34ebc2EnglishSymplectic Elements at Oxford2002Bäcklund, JCarlsen, SHöger, THolm, BFugger, LKihlberg, JBurkhardt, HHolmdahl, RRheumatoid arthritis (RA) is associated with certain MHC class II alleles and is characterized by a chronic autoimmune response in the joints. Using transgenic mice expressing human DR4 (DRB1*0401) and human CD4, but lacking endogenous MHC class II, we show that posttranslational glycosylation of type II collagen (CII) influences the level of T cell tolerance to this candidate cartilage-specific autoantigen. In such mice, the expression of human CII resulted in a tolerized murine T cell response to human CII. However, tolerance induction remained incomplete, preferentially deleting responses to the nonmodified CII 263-270 epitope, whereas T cell recognition of a glycosylated variant of this epitope was affected to a lesser degree. A similar dominance of T cell responses to CII-glycopeptides was recorded in a cohort of severely affected RA-patients (n = 14). Thus, RA T cells predominantly recognize the immunodominant CII peptide in its glycosylated form and may explain why previously it has been difficult to detect T cell responses to CII in RA patients. |
| spellingShingle | Bäcklund, J Carlsen, S Höger, T Holm, B Fugger, L Kihlberg, J Burkhardt, H Holmdahl, R Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis. |
| title | Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis. |
| title_full | Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis. |
| title_fullStr | Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis. |
| title_full_unstemmed | Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis. |
| title_short | Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis. |
| title_sort | predominant selection of t cells specific for the glycosylated collagen type ii epitope 263 270 in humanized transgenic mice and in rheumatoid arthritis |
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