Molecular chaperones are targets of autoimmunity in Ro(SS-A) immune mice

G. Kinoshita, A. W. Purcell, C. L. Keech, A. D. Farris, J. McCluskey, Tom P. Gordon

    Research output: Contribution to journalArticlepeer-review

    30 Citations (Scopus)


    We have used a murine model of experimental anti-Ro(SS-A) autoimmunity to dissect additional intermolecular interactions between the 52-kD Ro (Ro52) and 60-kD Ro (Ro60) autoantigens and molecular chaperones. Immune responses to members of the heat shock protein hsp70 and hsp90 families were measured by immunoblotting and ELISA in sera from mice immunized and boosted With purified recombinant Ro52, Ro60 and La (SS-B). All Ro52 and Ro60 immune sera immunoblotted the inducible glucose-regulated protein grp78 and hsp70 species but not constitutive hsc70 or hsp90. The kinetics of antibody production and reciprocal affinity purification experiments indicated that the grp78 and hsp70 responses were cross-reactive but distinct from immune responses to the primary Ro52 and Ro60 immunogens and the endoplasmic reticulum (ER)-resident chaperone calreticulin. No responses to molecular chaperones were detected in the La-immunized mice. Control immunizations indicated that the recruited grp78 and hsp70 responses were specific for the Ro proteins and not due to immunization with denatured protein. The rapid spreading of immunity to the inducible grp78 and hsp70 in Ro52- and Ro60-immunized mice suggests that these components may co-localize and physically associate under certain physiological conditions which may promote autoimmunization. The potential importance of the ER-resident chaperones grp78 and calreticulin is further supported by their co-localization with Ro in small apoptotic membrane blebs and the finding of a novel putative grp78 binding motif in the carboxyl- terminal region of Ro52.

    Original languageEnglish
    Pages (from-to)268-274
    Number of pages7
    JournalClinical and Experimental Immunology
    Issue number2
    Publication statusPublished - 1 Jan 1999


    • Autoimmunity
    • Chaperones
    • Ro(SS-A)


    Dive into the research topics of 'Molecular chaperones are targets of autoimmunity in Ro(SS-A) immune mice'. Together they form a unique fingerprint.

    Cite this