Self-peptides with intermediate capacity to bind and stabilize MHC class I molecules may be immunogenic.
Thirty self-peptides were selected on the basis of their predicted binding to H-2b molecules. The binding of peptides was ascertained experimentally by biochemical (KD measurements) and cellular [major histocompatibility complex class I (MHC-I) stabilization] assays. A weak, but significant, correlation between KD measurements and MHC-I stabilization was observed. Mice (n = 99) were immunized with individual peptides. Twenty-eight peptides were found to induce peptide-specific cytotoxic activity, and a total of 84 mice developed significant cytotoxic T lymphocyte (CTL) responses after immunization. Only one of the 21 mice immunized with high-affinity peptides developed a peptide-specific CTL response of 29 lytic units per 106 splenocytes, whereas 11 of the 42 mice immunized with intermediate-affinity peptides developed peptide-specific CTL responses at this level (P < 0.05). These observations suggest the absence of tolerance towards most MHC-I-restricted self-peptides and that strong antiself immunity can be generated preferentially towards self-peptides with an intermediate affinity for MHC-I. These data should be considered in the design of tumour vaccines based on MHC-I-binding self-peptides.
Andersen
M L M
ML
Laboratory of Cellular Immunology, Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Ruhwald
M
M
Nissen
M H
MH
Buus
S
S
Claesson
M H
MH
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D007108:Immune Tolerance; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D001324:Autoantigens; D006183:H-2 Antigens; D010455:Peptides