Autoantibodies against peptide-defined epitopes of T-cell receptors in retrovirally infected humans and mice.
Autoantibodies directed against peptide-defined epitopes of T-cell receptors occur in the serum of healthy humans with the levels and isotypic expression dependent upon physiological changes (aging, pregnancy) or upon the development of autoimmune disease. We carried out investigations of autoantibodies against Tcr peptide-defined epitopes in retroviral infections of humans (HIV-1) and mice (LP-BM5 strain of murine leukemia virus) to determine whether infection with these agents disrupted the regulation of the production of these antibodies. Retroviral infection in humans resulted in increased levels of autoantibody production against putative immunoregulatory regions of the Tcr beta chain (V beta CDR1 and Fr3), a result reflecting a disruption of regulation. In addition, antigenic mimicry was observed with a cross-reaction shared between the common portion of the V3 neutralizing loop of the HIV-1 gp120 molecule and the joining segment of T-cell receptors (J beta). Infection of mice with the defective retrovirus resulted in the induction of antibodies directed particularly against V beta CDR1 peptide-defined determinants. Analysis of the virally induced response to a set of 8 CDR1 peptide epitopes indicated a selectivity to the process. It was possible to partially reverse aberrant cytokine changes correlated with the onset of murine MAIDS by administration of T-cell receptor peptides in saline. These results show that retroviral infection in humans and mice has a profound dysfunctional effect on the regulation of autoantibodies to T-cell receptors. The function of these autoantibodies in the immunopathogenesis of acquired immunodeficiency remains to be determined.
Marchalonis
J J
JJ
University of Arizona, Tucson, USA.
Lake
D F
DF
Schluter
S F
SF
Dehghanpisheh
K
K
Watson
R R
RR
Ampel
N M
NM
Galgiani
J N
JN
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D009052:Leukemia Virus, Murine / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell; D012192:Retroviridae Infections / Q000276:immunology*
D001323:Autoantibodies; D016207:Cytokines; D000939:Epitopes; D010455:Peptides; D011948:Receptors, Antigen, T-Cell