Stimulation of human cytotoxic T cells with HIV-1-derived peptides presented by recombinant HLA-A2 peptide complexes |
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Authors: | Walter, JB Brander, C Mammen, M Garboczi, DN Kalams, SA Whitesides, GM Walker, BD Eisen, HN |
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Affiliation: | Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA. |
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Abstract: | HLA-A2 heavy chain and beta 2-microglobulin were expressed in Escherichiacoli, and refolded in the presence of peptides derived from HIV-1 RT andgag proteins. When recombinant HLA-A2 molecules were attached to cellslacking HLA-A2, the cells became susceptible to lysis by HLA-A2-restrictedcytotoxic T lymphocyte (CTL) clones specific for peptides derived from RTand gag proteins. Limiting dilution analyses of peripheral bloodmononuclear cells from HIV-1-infected individuals showed that therecombinant HLA-A2 peptide complexes covalently immobilized on microspheresstimulated the development of HLA-A2 peptide-specific CTL. PreformedHLA-peptide complexes may provide an alternative to immunization proceduresthat depend upon intracellular processing of antigen to elicit T cellresponses. |
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