Self-peptides with intermediate capacity to bind and stabilize MHC class I molecules may be immunogenic.

TY - JOUR

T1 - Self-peptides with intermediate capacity to bind and stabilize MHC class I molecules may be immunogenic.

AU - Andersen, M L M

AU - Ruhwald, M

AU - Nissen, Mogens Holst

AU - Buus, S

AU - Claesson, M H

N1 - Keywords: Animals; Autoantigens; Cytotoxicity, Immunologic; Female; H-2 Antigens; Immune Tolerance; Immunization; Mice; Mice, Inbred C57BL; Peptides; T-Lymphocytes, Cytotoxic; Thymus Gland

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 12542794

SN - 0301-6323

VL - 57

SP - 21

EP - 27

JO - Scandinavian Journal of Immunology, Supplement

JF - Scandinavian Journal of Immunology, Supplement

IS - 1

ER -