1.9 A structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen.
CAMPATH-1 antibodies have a long and successful history in the treatment of leukaemia, autoimmune disease and transplant rejection. The first antibody to undergo "humanisation", CAMPATH-1H, permits treatment with limited patient anti-globulin response. It recognises the CD52 antigen which...
Asıl Yazarlar: | , , , , |
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Materyal Türü: | Journal article |
Dil: | English |
Baskı/Yayın Bilgisi: |
1999
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_version_ | 1826293714870337536 |
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author | James, L Hale, G Waldmann, H Bloomer, A Waldman, H |
author_facet | James, L Hale, G Waldmann, H Bloomer, A Waldman, H |
author_sort | James, L |
collection | OXFORD |
description | CAMPATH-1 antibodies have a long and successful history in the treatment of leukaemia, autoimmune disease and transplant rejection. The first antibody to undergo "humanisation", CAMPATH-1H, permits treatment with limited patient anti-globulin response. It recognises the CD52 antigen which is a small glycosylphosphatidylinositol(GPI)-anchored protein expressed on lymphocytes and mediates cell depletion. We present the 1.9 A structure of the CAMPATH-1H Fab complexed [corrected] with an analogue of the antigenic determinant of CD52. Analysis of the CAMPATH-1H binding site reveals that in contrast to most antibodies CDR L3 plays a dominant role in antigen binding. Furthermore CDR H3, which is essential for effective antigen recognition in most antibodies, participates in only two main-chain interactions in CAMPATH-1H. The CAMPATH-1H binding site is highly basic; ionic interaction with the enthanolamine phosphate of the CD52 GPI anchor has long been hypothesised to be important in antigen binding. The structure reveals a number of important specific ionic interactions, including Lys53H but not Lys52bH as had previously been suggested. Prolonged treatment with CAMPATH-1H can lead to patient anti-idiotype responses which may be exacerbated by the unusually high number of basic residues in the antibody. This suggests that a strategy where redundant basic residues are replaced with neutral counterparts may be effective in further reducing the immunogenicity of this versatile and widely used antibody. |
first_indexed | 2024-03-07T03:34:25Z |
format | Journal article |
id | oxford-uuid:bbcfd706-8cca-4df1-bba5-0b1a97ff0ce9 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T03:34:25Z |
publishDate | 1999 |
record_format | dspace |
spelling | oxford-uuid:bbcfd706-8cca-4df1-bba5-0b1a97ff0ce92022-03-27T05:19:43Z1.9 A structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bbcfd706-8cca-4df1-bba5-0b1a97ff0ce9EnglishSymplectic Elements at Oxford1999James, LHale, GWaldmann, HBloomer, AWaldman, HCAMPATH-1 antibodies have a long and successful history in the treatment of leukaemia, autoimmune disease and transplant rejection. The first antibody to undergo "humanisation", CAMPATH-1H, permits treatment with limited patient anti-globulin response. It recognises the CD52 antigen which is a small glycosylphosphatidylinositol(GPI)-anchored protein expressed on lymphocytes and mediates cell depletion. We present the 1.9 A structure of the CAMPATH-1H Fab complexed [corrected] with an analogue of the antigenic determinant of CD52. Analysis of the CAMPATH-1H binding site reveals that in contrast to most antibodies CDR L3 plays a dominant role in antigen binding. Furthermore CDR H3, which is essential for effective antigen recognition in most antibodies, participates in only two main-chain interactions in CAMPATH-1H. The CAMPATH-1H binding site is highly basic; ionic interaction with the enthanolamine phosphate of the CD52 GPI anchor has long been hypothesised to be important in antigen binding. The structure reveals a number of important specific ionic interactions, including Lys53H but not Lys52bH as had previously been suggested. Prolonged treatment with CAMPATH-1H can lead to patient anti-idiotype responses which may be exacerbated by the unusually high number of basic residues in the antibody. This suggests that a strategy where redundant basic residues are replaced with neutral counterparts may be effective in further reducing the immunogenicity of this versatile and widely used antibody. |
spellingShingle | James, L Hale, G Waldmann, H Bloomer, A Waldman, H 1.9 A structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen. |
title | 1.9 A structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen. |
title_full | 1.9 A structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen. |
title_fullStr | 1.9 A structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen. |
title_full_unstemmed | 1.9 A structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen. |
title_short | 1.9 A structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen. |
title_sort | 1 9 a structure of the therapeutic antibody campath 1h fab in complex with a synthetic peptide antigen |
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