HLA-A2 subtypes are functionally distinct in peptide binding and presentation.
Nearly half of HLA-A2-positive individuals in African populations have a subtype of HLA-A2 other than the A*0201 allele. We have isolated the common African HLA-A2 subtype genes from Epstein-Barr virus-transformed B cell lines and have established stable class I reduced transfectants expressing thes...
| Hoofdauteurs: | , , , , , , , , |
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| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
1995
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| _version_ | 1826283100358836224 |
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| author | Barouch, D Friede, T Stevanović, S Tussey, L Smith, K Rowland-Jones, S Braud, V McMichael, A Rammensee, H |
| author_facet | Barouch, D Friede, T Stevanović, S Tussey, L Smith, K Rowland-Jones, S Braud, V McMichael, A Rammensee, H |
| author_sort | Barouch, D |
| collection | OXFORD |
| description | Nearly half of HLA-A2-positive individuals in African populations have a subtype of HLA-A2 other than the A*0201 allele. We have isolated the common African HLA-A2 subtype genes from Epstein-Barr virus-transformed B cell lines and have established stable class I reduced transfectants expressing these alleles. We have studied the peptide binding and presentation properties of A*0201, A*0202, A*0205, A*0214, and A*6901 by a combination of approaches: assaying direct binding of labeled synthetic peptides, studying the ability of antigen-specific cytotoxic T lymphocytes to recognize peptide-pulsed cells, and sequencing peptide pools and individual ligands eluted from cells. We find that A*0201-restricted peptides can also bind to A*0202 but do not bind strongly to the other alleles in this study. We show that some cytotoxic T lymphocytes can recognize all subtypes capable of binding an antigenic peptide, whereas others are subtype specific. Sequencing of eluted peptides reveals that A*0202 has a similar peptide motif to A*0201, but that A*0205, A*0214, and A*6901 have different motifs. These data strongly support a model in which residue 9 (Phe or Tyr) of the A2/A68/A69 molecules is a critical factor in determining the specificity of the B pocket of the major histocompatibility complex and the position 2 anchor residue of associated peptides. We conclude that a single-amino acid difference in the major histocompatibility complex can be sufficient to cause a dramatic change in the nature of bound peptides, implying that individuals with closely related HLA subtypes may present very different repertoires of antigenic peptides to T cells in an immune response. It is likely to be a general phenomenon that very similar class I subtypes will behave as functionally distinct HLA allotypes. |
| first_indexed | 2024-03-07T00:53:50Z |
| format | Journal article |
| id | oxford-uuid:87553ea7-78c0-4b2e-aa72-c0792a920c0c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:53:50Z |
| publishDate | 1995 |
| record_format | dspace |
| spelling | oxford-uuid:87553ea7-78c0-4b2e-aa72-c0792a920c0c2022-03-26T22:10:05ZHLA-A2 subtypes are functionally distinct in peptide binding and presentation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:87553ea7-78c0-4b2e-aa72-c0792a920c0cEnglishSymplectic Elements at Oxford1995Barouch, DFriede, TStevanović, STussey, LSmith, KRowland-Jones, SBraud, VMcMichael, ARammensee, HNearly half of HLA-A2-positive individuals in African populations have a subtype of HLA-A2 other than the A*0201 allele. We have isolated the common African HLA-A2 subtype genes from Epstein-Barr virus-transformed B cell lines and have established stable class I reduced transfectants expressing these alleles. We have studied the peptide binding and presentation properties of A*0201, A*0202, A*0205, A*0214, and A*6901 by a combination of approaches: assaying direct binding of labeled synthetic peptides, studying the ability of antigen-specific cytotoxic T lymphocytes to recognize peptide-pulsed cells, and sequencing peptide pools and individual ligands eluted from cells. We find that A*0201-restricted peptides can also bind to A*0202 but do not bind strongly to the other alleles in this study. We show that some cytotoxic T lymphocytes can recognize all subtypes capable of binding an antigenic peptide, whereas others are subtype specific. Sequencing of eluted peptides reveals that A*0202 has a similar peptide motif to A*0201, but that A*0205, A*0214, and A*6901 have different motifs. These data strongly support a model in which residue 9 (Phe or Tyr) of the A2/A68/A69 molecules is a critical factor in determining the specificity of the B pocket of the major histocompatibility complex and the position 2 anchor residue of associated peptides. We conclude that a single-amino acid difference in the major histocompatibility complex can be sufficient to cause a dramatic change in the nature of bound peptides, implying that individuals with closely related HLA subtypes may present very different repertoires of antigenic peptides to T cells in an immune response. It is likely to be a general phenomenon that very similar class I subtypes will behave as functionally distinct HLA allotypes. |
| spellingShingle | Barouch, D Friede, T Stevanović, S Tussey, L Smith, K Rowland-Jones, S Braud, V McMichael, A Rammensee, H HLA-A2 subtypes are functionally distinct in peptide binding and presentation. |
| title | HLA-A2 subtypes are functionally distinct in peptide binding and presentation. |
| title_full | HLA-A2 subtypes are functionally distinct in peptide binding and presentation. |
| title_fullStr | HLA-A2 subtypes are functionally distinct in peptide binding and presentation. |
| title_full_unstemmed | HLA-A2 subtypes are functionally distinct in peptide binding and presentation. |
| title_short | HLA-A2 subtypes are functionally distinct in peptide binding and presentation. |
| title_sort | hla a2 subtypes are functionally distinct in peptide binding and presentation |
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