In Vivo Cytotoxic T Lymphocyte Elicitation by Mycobacterial Heat Shock Protein 70 Fusion Proteins Maps to a Discrete Domain and Is CD4+ T Cell Independent

doi:10.1084/jem.191.2.403

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© The Rockefeller University Press, 0022-1007/2000/1/403/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 2, January 17, 2000 403-408

Brief Definitive Report

In Vivo Cytotoxic T Lymphocyte Elicitation by Mycobacterial Heat Shock Protein 70 Fusion Proteins Maps to a Discrete Domain and Is CD4⁺ T Cell Independent

Qian Huang^a, Joan F.L. Richmond^a, Kimiko Suzue^a, Herman N. Eisen^b,c, and Richard A. Young^a,b
^a Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142
^b Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
^c Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Correspondence to: Richard A. Young, Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142. Tel:617-258-5218 Fax:617-258-0376 E-mail:young{at}wi.mit.edu.

To gain insights into the mechanisms by which soluble heat shockprotein (hsp) fusions can elicit CD8⁺ cytotoxic T lymphocytes(CTLs) against the fusion partner, mycobacterial (Mycobacteriumtuberculosis) hsp70 was dissected to ascertain whether a particularhsp domain is necessary, and knockout mice were used to determinewhether the fusion protein's immunogenicity is dependent onCD4⁺ T lymphocytes. We found that the ability to elicit CD8⁺CTLs depends on a discrete 200–amino acid protein domain,indicating that the fusion protein's immunogenicity for CD8⁺T cells does not require coupled chaperone function or peptidebinding. Further, we found that ovalbumin (OVA).hsp70 fusionprotein elicited anti-OVA CD8⁺ CTLs about equally well in CD4knockout and wild-type C57BL/6 mice, and also when the hsp70was of murine (self) origin. The ability of hsp70 fusion proteinsto elicit CD4-independent CTL responses suggests that hsp70fusion proteins may be useful for immunological prophylaxisand therapy against disease in CD4⁺ T cell–deficient individuals.

Key Words: CD8⁺, CD4⁺, domain, knockout, vaccine

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