Reconstitution of antigen presentation in HLA class I-negative cancer cells with peptide-beta2m fusion molecules.
Engineered MHC-peptide targets capable of inducing recognition by CTL may prove useful in designing vaccines for infectious disease and cancer. We tested whether peptides directly linked to beta2-microglobulin (beta2m) could complex with human HLA class I heavy chain, and could be recognized by huma...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2001
|
| _version_ | 1797060376959909888 |
|---|---|
| author | Tafuro, S Meier, U Dunbar, P Jones, E Layton, G Hunter, MG Bell, J Mcmichael, A |
| author_facet | Tafuro, S Meier, U Dunbar, P Jones, E Layton, G Hunter, MG Bell, J Mcmichael, A |
| author_sort | Tafuro, S |
| collection | OXFORD |
| description | Engineered MHC-peptide targets capable of inducing recognition by CTL may prove useful in designing vaccines for infectious disease and cancer. We tested whether peptides directly linked to beta2-microglobulin (beta2m) could complex with human HLA class I heavy chain, and could be recognized by human CTL, both as soluble reagents and as cell surface constituents. An HLA-A2-restricted peptide epitope was physically linked to the N terminus of human beta2m. This fusion protein refolded efficiently in vitro with HLA-A2 heavy chain, and when multimerized, the resultant complexes ("fusamers") bound specifically to appropriate CTL clones. These fused peptide/MHC complexes were as efficient as standard tetrameric peptide/MHC complexes in recognizing antigen-specific CTL. When the fusion protein was delivered to target cells using a retroviral vector, these cells were recognized and killed by appropriate CTL clones. Efficient sensitization to CTL lysis was achieved in TAP-negative and beta2m-negative cell lines, as well as in unmutated B cell lines, proving that such constructs may be effective in inducing CTL even when the MHC class I pathway has been disrupted. Specific peptides covalently linked to beta2m and delivered via retroviral vectors may be useful reagents for in vivo priming of CTL against epitopes of clinical relevance. |
| first_indexed | 2024-03-06T20:16:16Z |
| format | Journal article |
| id | oxford-uuid:2c3dd7d4-70f8-4364-997d-8ef3f8826943 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:16:16Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:2c3dd7d4-70f8-4364-997d-8ef3f88269432022-03-26T12:35:50ZReconstitution of antigen presentation in HLA class I-negative cancer cells with peptide-beta2m fusion molecules.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2c3dd7d4-70f8-4364-997d-8ef3f8826943EnglishSymplectic Elements at Oxford2001Tafuro, SMeier, UDunbar, PJones, ELayton, GHunter, MGBell, JMcmichael, AEngineered MHC-peptide targets capable of inducing recognition by CTL may prove useful in designing vaccines for infectious disease and cancer. We tested whether peptides directly linked to beta2-microglobulin (beta2m) could complex with human HLA class I heavy chain, and could be recognized by human CTL, both as soluble reagents and as cell surface constituents. An HLA-A2-restricted peptide epitope was physically linked to the N terminus of human beta2m. This fusion protein refolded efficiently in vitro with HLA-A2 heavy chain, and when multimerized, the resultant complexes ("fusamers") bound specifically to appropriate CTL clones. These fused peptide/MHC complexes were as efficient as standard tetrameric peptide/MHC complexes in recognizing antigen-specific CTL. When the fusion protein was delivered to target cells using a retroviral vector, these cells were recognized and killed by appropriate CTL clones. Efficient sensitization to CTL lysis was achieved in TAP-negative and beta2m-negative cell lines, as well as in unmutated B cell lines, proving that such constructs may be effective in inducing CTL even when the MHC class I pathway has been disrupted. Specific peptides covalently linked to beta2m and delivered via retroviral vectors may be useful reagents for in vivo priming of CTL against epitopes of clinical relevance. |
| spellingShingle | Tafuro, S Meier, U Dunbar, P Jones, E Layton, G Hunter, MG Bell, J Mcmichael, A Reconstitution of antigen presentation in HLA class I-negative cancer cells with peptide-beta2m fusion molecules. |
| title | Reconstitution of antigen presentation in HLA class I-negative cancer cells with peptide-beta2m fusion molecules. |
| title_full | Reconstitution of antigen presentation in HLA class I-negative cancer cells with peptide-beta2m fusion molecules. |
| title_fullStr | Reconstitution of antigen presentation in HLA class I-negative cancer cells with peptide-beta2m fusion molecules. |
| title_full_unstemmed | Reconstitution of antigen presentation in HLA class I-negative cancer cells with peptide-beta2m fusion molecules. |
| title_short | Reconstitution of antigen presentation in HLA class I-negative cancer cells with peptide-beta2m fusion molecules. |
| title_sort | reconstitution of antigen presentation in hla class i negative cancer cells with peptide beta2m fusion molecules |
| work_keys_str_mv | AT tafuros reconstitutionofantigenpresentationinhlaclassinegativecancercellswithpeptidebeta2mfusionmolecules AT meieru reconstitutionofantigenpresentationinhlaclassinegativecancercellswithpeptidebeta2mfusionmolecules AT dunbarp reconstitutionofantigenpresentationinhlaclassinegativecancercellswithpeptidebeta2mfusionmolecules AT jonese reconstitutionofantigenpresentationinhlaclassinegativecancercellswithpeptidebeta2mfusionmolecules AT laytong reconstitutionofantigenpresentationinhlaclassinegativecancercellswithpeptidebeta2mfusionmolecules AT huntermg reconstitutionofantigenpresentationinhlaclassinegativecancercellswithpeptidebeta2mfusionmolecules AT bellj reconstitutionofantigenpresentationinhlaclassinegativecancercellswithpeptidebeta2mfusionmolecules AT mcmichaela reconstitutionofantigenpresentationinhlaclassinegativecancercellswithpeptidebeta2mfusionmolecules |