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An immunodominant CD4⁺ T cell site on the nucleocapsid protein of murine coronavirus contributes to protection against encephalomyelitis

Heiner Körner

Institute of Virology and Immunobiology, University of Würzburg, Versbacher Strae 7, 7078 Würzburg, Germany

The murine coronavirus neurotropic strain JHM (MHV-JHM) nucleocapsid (N) protein induces a strong T-helper cell response in Lewis rats. It has been shown previously that N-specific CD4⁺ T cells can confer protection against acute disease upon transfer to otherwise lethally infected rats. To define the major antigenic regions that elicit this T cell response, truncated fragments of N protein were expressed from a bacterial expression vector and employed as T cell antigens. Lymphocytes from either MHV-JHM-infected or immunized rats were stimulated in culture with virus antigen, grown and tested for their specificity to the N protein fragments. The carboxy-terminally located C4-N fragment (95 amino acids) induced the most pronounced proliferative response irrespective of whether the lymphocyte culture was derived from immunized or MHV-JHM-infected rats. We established T cell lines specific for the truncated N protein fragments and tested their potential to mediate protection by transfer experiments. Only the T cell line C4-N and the T cell line specific for the full-length N protein were protective. By contrast, all truncated N protein fragments elicited a humoral immune response and contained antigenic sites recognized by antibodies from diseased rats.

Present address: Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, NSW 2006, Australia.

Received 15 December 1992; accepted 19 February 1993.

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