Epitope specificity and Ia restriction of T cell responses to insulin in a system of complementing Ir genes: analysis with primed lymph node T cells and a long-term cultured T cell line.

6533b7d0fe1ef96bd125ae37

RESEARCH PRODUCT

Epitope specificity and Ia restriction of T cell responses to insulin in a system of complementing Ir genes: analysis with primed lymph node T cells and a long-term cultured T cell line.

subject

Male T cell T-Lymphocytes Immunology Cell Genes MHC Class II Mice Inbred Strains Biology Lymphocyte Activation Epitope Cell Line Epitopes Mice medicine Immunology and Allergy Animals Insulin Gene Genetics Genetic Complementation Test Histocompatibility Antigens Class II T lymphocyte Molecular biology In vitro Complementation medicine.anatomical_structure Cell culture Female Immunization

description

The antibody response of (H-2b X H-2k)F1 mice to pig insulin (PI) has previously been shown to be under the control of H-2-linked, complementing Ir genes. In addition, this response was reported to depend on the genetic background of the parental strains (Keck, K., Eur. J. Immunol. 1977. 7: 811). Here it is demonstrated that the secondary in vitro response of proliferating T cells shows the same dependence on H-2-linked Ir genes yet an influence of the background genes could not be detected. The complementing genes were mapped to the Kb, I-Ab and Kk, I-Ak regions. For restimulation of F1 T cells by PI, the Ir genes of both parental chromosomes have to be expressed in the same antigen-presenting cell, suggesting complementation at the molecular rather than at a cell interaction level. With a long-term cultured, PI-specific T cell line (ST2) of (B10 X B10.BR)F1 origin the complementation data could be confirmed by mapping the Ia restriction elements to Kb, I-Ab and I-Ak. The reactivity pattern of this line towards species variants of insulin and the isolated A and B polypeptide chains in the presence of syngeneic accessory cells suggests that the glutamic acid residue in position 4 of the A polypeptide chain (Asp in mouse insulin) is essential for recognition in conjunction with an (I-Ab X I-Ak)F1 hybrid Ia complex. I-Ab-encoded molecules carrying specificity Ia. W39 which, according to Rosenwasser, L. J. and Huber, B. T. are essential for the presentation of BI to (CBA/N X C57BL/6)F1 T cells, are not required as components of the F1-unique restriction element recognized by the F1 T cells of the ST2 line in conjunction with PI. This is indicated by the fact that accessory cells of (CBA/N X B10)F1 hybrids, regardless of their sex, could present PI as well as beef, sheep and horse insulin to the F1-restricted ST2 cells.

year	journal	country	edition	language
1983-09-01	European journal of immunology

10.1002/eji.1830130911 https://pubmed.ncbi.nlm.nih.gov/6193966