Immunization with glycosylated Kb-binding peptides generates carbohydrate-specific, unrestricted cytotoxic T cells

Ussama M. Abdel-Motal, Louise Berg, Anders Rosén, Marita Bengtsson, Cristopher J. Thorpe, Jan Kihlberg, Jan Dahmén, Göran Magnusson, Karl Anders Karlsson, Mikael Jondal

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Abstract

Cytotoxic T cells (CTL) recognize target proteins as short peptides presented by major histocompatibility complex (MHC) class I restriction elements. However, there is also evidence for peptide-independent T cell receptor (TCR) recognition of target proteins and non-protein structures. How such T cell responses are generated is presently unclear. We generated carbohydrate (CHO)-specific, MHC-unrestricted CTL responses by coupling di- and trisaccharides to Kb- or Db-binding peptides for direct immunization in mice. Four peptides and three CHO have been analyzed with the CHO either in terminal or central positions on the carrier peptide. With two of these glycopeptides, with galabiose (Galα1-4Gal;Gal2) bound to a homocysteine (via an ethylene spacer arm) in position 4 or 6 in a vesicular stomatitis virus nucleoprotein-derived peptide (RGYVYQGL binding to Kb), CTL were generated which preferentially killed target cells treated with glycopeptide compared to those treated with the core peptide. Polyclonal CTL were also found to kill target cells expressing the same Gal, epitope in a glycolipid. By fractionation of CTL, preliminary data indicate that glycopeptide-specific Kb-restricted CTL and unrestricted CHO-specific CTL belong to different T cell populations with regard to TCR expression. The results demonstrate that hapten-specific unrestricted CTL responses can be generated with MHC class I-binding carrier peptides. Different models that might explain the generation of such responses are discussed.

Original languageEnglish
Pages (from-to)544-551
Number of pages8
JournalEuropean Journal of Immunology
Volume26
Issue number3
DOIs
Publication statusPublished - 1 Mar 1996

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Keywords

  • Carbohydrate
  • Cytotoxic T lymphocyte
  • Glycopeptide
  • Major histocompatibility complex class I

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Abdel-Motal, U. M., Berg, L., Rosén, A., Bengtsson, M., Thorpe, C. J., Kihlberg, J., Dahmén, J., Magnusson, G., Karlsson, K. A., & Jondal, M. (1996). Immunization with glycosylated Kb-binding peptides generates carbohydrate-specific, unrestricted cytotoxic T cells. European Journal of Immunology, 26(3), 544-551. https://doi.org/10.1002/eji.1830260307