Induction of class I MHC-restricted, peptide-specific cytolytic T lymphocytes by peptide priming in vivo

• Published in: The Journal of immunology (1950) Vol. 143; no. 4; pp. 1094 - 1100
• Main Authors: Ishioka, GY, Colon, S, Miles, C, Grey, HM, Chesnut, RW
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-08-1989
• Subjects: Animals; Antigens - administration & dosage; Antigens - immunology; Cytotoxicity, Immunologic; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; Injections, Intraperitoneal; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Ovalbumin - administration & dosage; Ovalbumin - immunology; Peptide Fragments - administration & dosage; Peptide Fragments - immunology; T-Lymphocytes, Cytotoxic - classification; T-Lymphocytes, Cytotoxic - immunology; Trypsin
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.143.4.1094

The present study investigated the possibility that protein Ag fragments in the form of peptides could serve as the priming Ag in the generation of a MHC class I-restricted immune response. Trypsin-digested chicken ovalbumin (OVA-TD) fragments were used as the model Ag. The results demonstrate the peptides within OVA-TD, when injected into C57BL/6 mice, could prime T cells which lysed H-2b Ia-EL4 target cells in an OVA-TD-specific manner. In contrast to priming with OVA-TD, immunization of mice with intact OVA did not lead to generation of CTL against OVA-TD or OVA. Furthermore, target cells sensitized with intact OVA failed to be recognized by OVA-peptide-specific CTL indicating that the target cells serving as APC were unable to generate the relevant peptide determinants recognized by the T cells. These results support the idea that the processing pathway within APC for class I-restricted T cells may differ from that used for class II-restricted T cells. Using OVA-TD-specific CTL clones (phenotypically Thy 1+, CD8+, CD4-, Pgp-1+) isolated from primed animals to screen OVA-TD fractions separated by HPLC, two T cell peptide determinants were identified corresponding to OVA sequences 111-122 and 370-381. Both determinants were recognized by CTL clones in the context of the H-2Db molecule.