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 position on the carrier
peptide. With two of these
glycopeptides, with
galabiose (Gal alpha 1-4Gal; 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 Gal2
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.