Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2.
The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class I/peptide b...
| Auteurs principaux: | , , , , , , , , |
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| Format: | Journal article |
| Langue: | English |
| Publié: |
1997
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| _version_ | 1826305703508180992 |
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| author | Gao, G Tormo, J Gerth, U Wyer, JR McMichael, A Stuart, D Bell, J Jones, E Jakobsen, B |
| author_facet | Gao, G Tormo, J Gerth, U Wyer, JR McMichael, A Stuart, D Bell, J Jones, E Jakobsen, B |
| author_sort | Gao, G |
| collection | OXFORD |
| description | The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class I/peptide by binding to the class I molecule. Here we report the crystal structure at 2.7 A resolution of a complex between CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with the alpha2 and alpha3 domains of HLA-A2 and also contacting beta2-microglobulin. A flexible loop of the alpha3 domain (residues 223-229) is clamped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction, precluding the binding of a second MHC molecule. The position of the alpha3 domain is different from that in uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2 complex, but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in alpha3 may provide a synergistic modulation of affinity, the binding of CD8 to MHC is clearly consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC interactions. |
| first_indexed | 2024-03-07T06:36:52Z |
| format | Journal article |
| id | oxford-uuid:f7f37f0a-4c78-4e71-8319-1df1f00cb1ee |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:36:52Z |
| publishDate | 1997 |
| record_format | dspace |
| spelling | oxford-uuid:f7f37f0a-4c78-4e71-8319-1df1f00cb1ee2022-03-27T12:46:37ZCrystal structure of the complex between human CD8alpha(alpha) and HLA-A2.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f7f37f0a-4c78-4e71-8319-1df1f00cb1eeEnglishSymplectic Elements at Oxford1997Gao, GTormo, JGerth, UWyer, JRMcMichael, AStuart, DBell, JJones, EJakobsen, BThe dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class I/peptide by binding to the class I molecule. Here we report the crystal structure at 2.7 A resolution of a complex between CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with the alpha2 and alpha3 domains of HLA-A2 and also contacting beta2-microglobulin. A flexible loop of the alpha3 domain (residues 223-229) is clamped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction, precluding the binding of a second MHC molecule. The position of the alpha3 domain is different from that in uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2 complex, but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in alpha3 may provide a synergistic modulation of affinity, the binding of CD8 to MHC is clearly consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC interactions. |
| spellingShingle | Gao, G Tormo, J Gerth, U Wyer, JR McMichael, A Stuart, D Bell, J Jones, E Jakobsen, B Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. |
| title | Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. |
| title_full | Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. |
| title_fullStr | Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. |
| title_full_unstemmed | Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. |
| title_short | Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. |
| title_sort | crystal structure of the complex between human cd8alpha alpha and hla a2 |
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