Cellular immunity to encephalitogenic peptide in tumour-bearing mice

Abstract

Summary.-Mice bearing a methylcholanthrene-induced tumour were tested for their cell-mediated reactivity to the experimental allergic encephalomyelitis (EAE) peptide of human myelin basic protein (MBP) in the leucocyte adherence inhibition (LAI) test. Tested over a range of peptide concentrations, peritoneal cells (PC) from tumour-bearing mice exhibited optimal adherence inhibition at 640 ng/ml; PC from normal and parasite-infected mice were unreactive. The EAE peptide also stimulated PC from tumour-bearing mice in the E-rosette augmentation (ERA) test and in the macrophage migration inhibition (MMI) test. MMI appeared to be the most sensitive assay, in that significant reaction at peptide concentrations well below those giving significant LAI and ERA. LAI reactivity to the peptide was detected 5 days after tumour transplantation, and continued to be detectable even with very large tumours. In vitro assays were confirmed by demonstration of EAE peptide recognition in vivo, in tumour-bearing and tumour-excised mice, using the delayedtype hypersensitivity reaction. The present experiments demonstrate an antigenic determinant in murine tumours, similar to the well-characterized EAE peptide of human MBP, and establish an animal model for study and characterization of common tumour-associated antigens.

Restricted Activity of Serum Blocking Factors Related to a Common Tumour Antigen in Mice

“…1). Lack of reactivity at high concentrations of the peptide was always observed, and has been dis cussed elsewhere [1], We have preferred to use the LAI assay because of its rapidity, convenience and re producibility, but have shown previously that other techniques of CMI gave similar results [1], LAI. in the form used here with murine tumour antigens, reflects the activity of T lymphocytes [17].…”

“…Although excess antigen is known to suppress in vitro reactions of CMI [1,23,24], the blocking factor detected here must be a substance other than excess circulating tumour antigen, since the antigen used is not strain-restricted in its action. The time of appearance of blocking factor related to EAE peptide was delayed in comparison to previous findings by others.…”

“…In a previous paper [1], mice bearing a chemically induced tumour were shown to develop cell-mediated immunity (CMI) to a simple antigenic determinant. This determinant, well known as the region of human myelin basic protein (MBP) inducing experimental allergic encephalomyelitis (EAE) in guineapigs, is a nonapeptide of defined structure.…”

An Approach to Searching Protein Sequences for Superfamily Relationships or Chance Similarities Relevant to the Molecular Mimicry Hypothesis: Application to the Basic Proteins of Myelin

“…(1 985) from synaptosomes and shown to share some chemical and immunochemical properties with MBP, and a cancer cell basic protein, identified in a variety of malignant tumors (Field and Caspary, 1970) and found to react with lymphocytes from cancer patients in a manner similar to MBP (Carnegie et al, 1973;Yong and Halliday, 1982).…”

Conformation of a heptadecapeptide comprising the segment encephalitogenic in rhesus monkey

“…A cell-mediated reactivity to MBP and to the guinea pig determinant has been reported in tumor-bearing mice but not in controls (Yong & Halliday, 1982). The peptide comprising the first nine residues of the monkey encephalitogen shows similar reactivity in tumor-bearing mice (W. J. Halliday, personal communication).…”