2001/02/01 by Sabrina Tafuro, Ute-Christiane Meier, Ute‐Christiane Meier +11 · 26 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Antigen #Antigen presentation #Biochemistry #Biology #CTL* #Cell biology #Cytotoxic T cell #Epitope #Fusion protein #Gene #Human leukocyte antigen #Immunology #Immunotherapy and Immune Responses #In vitro #MHC class I #Major histocompatibility complex #Molecular biology #Peptide #Recombinant DNA #T-cell and B-cell Immunology #Virology #vaccines and immunoinformatics approaches
paper · doi:10.1002/1521-4141(200102)31:2<440::aid-immu440>3.0.co;2-0
published in European Journal of Immunology 31(2), 440-449 (Wiley)
openalex publication_date 2001/02/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/26
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.