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In vitro priming of human lymphocytes to heterologous insulins.
- Source :
-
Journal of immunological methods [J Immunol Methods] 1989 Jun 21; Vol. 120 (2), pp. 159-65. - Publication Year :
- 1989
-
Abstract
- We have developed an in vitro priming assay in which peripheral blood lymphocytes from normal subjects are primed with insulin for 14 days prior to challenge with insulin in conjunction with autologous antigen-presenting cells for a further 5 days. Sheep, beef and pork insulins possess, respectively, four, three and one amino acid differences from the human molecule (out of a total of 51 residues) and the magnitude of the response to priming correlates with the degree of sequence variation. Although human insulin produces little response, priming with heterologous insulins readily induces auto-immunization on secondary challenge. The response to porcine priming was enhanced if the secondary cultures were challenged with bovine or ovine insulin, i.e., a heteroclitic response was observed. Individual donors differ in their response to priming and high responders possess the HLA-DR7 glycoprotein more frequently than low responders. This is in keeping with previous studies on antibody production in vivo and probably relates to the ease with which individual class II glycoproteins complex with processed antigen and stimulate T cells. This method has considerable potential for screening novel insulin molecules and formulations and should facilitate the mapping of helper and suppressor epitopes as well as the identification of agretopes involved in the presentation of insulin to T cells.
- Subjects :
- Animals
Antigen-Presenting Cells immunology
B-Lymphocytes immunology
Cattle
Cells, Cultured
Dose-Response Relationship, Immunologic
HLA Antigens analysis
HLA-DR Antigens analysis
Immunologic Memory
In Vitro Techniques
Macrophages immunology
Sheep
Species Specificity
Structure-Activity Relationship
Swine
Time Factors
Insulin immunology
Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1759
- Volume :
- 120
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of immunological methods
- Publication Type :
- Academic Journal
- Accession number :
- 2661692
- Full Text :
- https://doi.org/10.1016/0022-1759(89)90237-8