AN IMMUNODOMINANT CD4-CELL SITE ON THE NUCLEOCAPSID PROTEIN OF MURINECORONAVIRUS CONTRIBUTES TO PROTECTION AGAINST ENCEPHALOMYELITIS( T)

The murine coronavirus neurotropic strain JHM (MHV-JHM) nucleocapsid ( N) protein induces a strong T-helper cell response in Lewis rats. It h as been shown previously that N-specific CD4+ T cells can confer prote ction against acute disease upon transfer to otherwise lethally infect ed rats. To define the major antigenic regions that elicit this T cell response, truncated fragments of N protein were expressed from a bact erial expression vector and employed as T cell antigens. Lymphocytes f rom either MHV-JHM-infected or immunized rats were stimulated in cultu re with virus antigen, grown and tested for their specificity to the N protein fragments. The carboxy-terminally located C4-N fragment (95 a mino acids) induced the most pronounced proliferative response irrespe ctive of whether the lymphocyte culture was derived from immunized or MHV-JHM-infected rats. We established T cell lines specific for the tr uncated N protein fragments and tested their potential to mediate prot ection by transfer experiments. Only the T cell line C4-N and the T ce ll line specific for the full-length N protein were protective. By con trast, all truncated N protein fragments elicited a humoral immune res ponse and contained antigenic sites recognized by antibodies from dise ased rats.