The effects of polyamines on the immunogenicity of polynucleotides

TY - JOUR

T1 - The effects of polyamines on the immunogenicity of polynucleotides

AU - Gunnia, Uma B.

AU - Thomas, Thresia

AU - Thomas, T. J.

N1 - Funding Information: This work was supported, in part,, by the National Institutes of Health through research grants AR 39020 and CA 42439, by the Foundation of UMDNJ and the Arthritis Foundation New Jersey Chapter. All correspondence and requests for reprints should be addressed to: T. J. Thomas, Ph.D., Laboratory Director, Clinical Research Center, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903-0019.

PY - 1991

Y1 - 1991

N2 - Polyamines-putrescine, spermidine, and spermine-are small organic cations that are present in all living cells. Recent studies revealed that polyamines could provoke a left-handed Z-DNA conformation in poly(dA-dC).poly(dG-dT) and related alternating purine-pyrimidine sequences. In order to examine whether polyamine-induced Z-DNA conformation of poly(dA-dC).poly(dG-dT) is capable of eliciting anti-Z-DNA antibodies, we immunized rabbits with poly(dA-dC).poly(dG-dT) in the presence and absence of spermidine and spermine. Rabbits immunized with the polynucleotide alone produced antibodies reacting toward poly(dA-dC).poly(dG-dT) and heat-denatured calf thymus DNA (ssDNA). In contrast, immunization with poly(dA-dC).poly(dG-dT) complexed with spermidine or spermine produced antibodies reacting with Z-DNA in addition to those binding toward poly(dA-dC).poly(dG-dT) and ssDNA. Antibodies elicited by polynucleotide polyamine complexes had no reactivity toward polyamines. Solution inhibition studies suggested that anti-poly(dA-dC).poly(dG-dT), anti-ssDNA and anti-Z-DNA antibodies are distinct populations that favor each one of these antigens. Our results suggest that natural polyamines are capable of altering the immunogenicity of polynucleotides by mechanisms involving the stabilization of Z-DNA conformation. This result may have implications in the recent findings of high levels of polyamines and anti-Z-DNA antibodies in the sera of lupus patients and autoimmune mice.

AB - Polyamines-putrescine, spermidine, and spermine-are small organic cations that are present in all living cells. Recent studies revealed that polyamines could provoke a left-handed Z-DNA conformation in poly(dA-dC).poly(dG-dT) and related alternating purine-pyrimidine sequences. In order to examine whether polyamine-induced Z-DNA conformation of poly(dA-dC).poly(dG-dT) is capable of eliciting anti-Z-DNA antibodies, we immunized rabbits with poly(dA-dC).poly(dG-dT) in the presence and absence of spermidine and spermine. Rabbits immunized with the polynucleotide alone produced antibodies reacting toward poly(dA-dC).poly(dG-dT) and heat-denatured calf thymus DNA (ssDNA). In contrast, immunization with poly(dA-dC).poly(dG-dT) complexed with spermidine or spermine produced antibodies reacting with Z-DNA in addition to those binding toward poly(dA-dC).poly(dG-dT) and ssDNA. Antibodies elicited by polynucleotide polyamine complexes had no reactivity toward polyamines. Solution inhibition studies suggested that anti-poly(dA-dC).poly(dG-dT), anti-ssDNA and anti-Z-DNA antibodies are distinct populations that favor each one of these antigens. Our results suggest that natural polyamines are capable of altering the immunogenicity of polynucleotides by mechanisms involving the stabilization of Z-DNA conformation. This result may have implications in the recent findings of high levels of polyamines and anti-Z-DNA antibodies in the sera of lupus patients and autoimmune mice.

UR - https://www.scopus.com/pages/publications/0025949078

UR - https://www.scopus.com/pages/publications/0025949078#tab=citedBy

U2 - 10.3109/08820139109057760

DO - 10.3109/08820139109057760

M3 - Article

C2 - 1937581

SN - 0882-0139

VL - 20

SP - 337

EP - 350

JO - Immunological Investigations

JF - Immunological Investigations

IS - 4

ER -