An immunodominant CD4+ T cell site on the nucleocapsid protein of murine coronavirus contributes to protection against encephalomyelitis.
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.
Institute of Virology and Immunobiology, University of Würzburg, Germany.
H
H
Wege
A
A
Schliephake
H
H
Körner
E
E
Flory
H
H
Wege
D000818:Animals; D000833:Animals, Suckling; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology*; D015153:Blotting, Western; D015704:CD4 Antigens / Q000378:metabolism*; D002213:Capsid / Q000276:immunology*; D003332:Coronaviridae / Q000276:immunology* / Q000472:pathogenicity; D003333:Coronaviridae Infections / Q000276:immunology* / Q000517:prevention & control; D004679:Encephalomyelitis / Q000276:immunology* / Q000517:prevention & control; D004797:Enzyme-Linked Immunosorbent Assay; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D015704:CD4 Antigens; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014765:Viral Vaccines