Synthetic polypeptides and antibodies related to Epstein-Barr virus nuclear antigen

Abstract

Antigens, immunogens, inocula, antibodies, diagnostic methods and systems relating to Epstein-Barr virus nuclear antigen (EBNA) are disclosed. Each of the compounds, compositions, methods or systems contains a synthetic, random copolymer polypeptide having about 6 to about 40 residues, or an antibody containing site that immunoreacts with such a polypeptide. The polypeptide includes the five amino acid residue sequence -Gly-R 1 -Gly-R 2 -Gly-, wherein R 1 and R 2 are the same or different amino acid residues selected from the group consisting of Ala, Asn, Arg, Gly, Leu, Pro, Ser, and Thr, with the provision that R 1 and R 2 are not both Gly. The polypeptide contains at least 25 mole percent Gly residues, and when linked to a carrier and introduced in an effective amount into a mammalian host is capable of inducing production of antibodies that immunoreact with EBNA.

What is claimed is: 
     
       1. A synthetic polypeptide .[.having.]. .Iadd.that consists essentially of up to about 20 residues and includes .Iaddend.an amino acid residue sequence, taken from left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:   .[.H-.]. Arg-Ala-Arg-Gly-Arg-Gly-Arg-Gly-Arg-Gly-Glu-Lys-Arg-Pro-Met.[.-OH.].;     .Iadd.and .Iaddend.the pharmaceutically acceptable salts thereof, .[.and antigenically related variants thereof.]. .Iadd.said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend.   
     
     
       2. A synthetic polypeptide .[.having.]. .Iadd.that consists essentially of up to about 20 residues and includes .Iaddend.an amino acid residue sequence, taken from left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:   .[.H-.]. Ile-Met-Ser-Asp-Glu-Gly-Pro-Gly-Thr-Gly-Asn-Gly-Leu-Gly-Glu.[.-OH.].;     .Iadd.and .Iaddend.the pharmaceutically acceptable salts thereof, .[.and antigenically related variants thereof.]. .Iadd.said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend.   
     
     
       3. A synthetic polypeptide .[.having.]. .Iadd.that consists essentially of up to about 20 residues and includes .Iaddend.an amino acid residue sequence, taken from left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:   .[.H-.]. Pro-Gly-Ala-Pro-Gly-Gly-Ser-Gly-Ser-Gly-Pro.[.-OH.].;     .Iadd.and .Iaddend.the pharmaceutically acceptable salts thereof, .[.and antigenically related variants thereof.]. .Iadd.said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend.   
     
     
       4. A synthetic polypeptide .[.having.]. .Iadd.that consists essentially of up to about 20 residues and includes .Iaddend.an amino acid residue sequence, taken from left to right and in the direction of the amino-terminus to carboxy-terminus, represented by the formula:   .[.H-.]. Gly-Gly-Gly-Ala-Gly-Ala-Gly-Gly-Ala-Gly-Ala-Gly-Gly-Gly-Gly-Arg.[.-OH.].;     .Iadd.and .Iaddend.the pharmaceutically acceptable salts thereof, .[.and antigenically related variants thereof.]. .Iadd.said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend.   
     
     
       5. A synthetic polypeptide .[.having.]. .Iadd.that consists essentially of up to about 20 residues and includes .Iaddend.an amino residue sequence, taken from left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:   .[.H-.]. Lys-Gly-Thr-His-Gly-Gly-Thr-Gly-Ala-Gly-Ala-Gly-Ala-Gly-Gly-Ala-Gly-Ala-Gly.[.-OH.].;     .Iadd.and .Iaddend.the pharmaceutically acceptable salts thereof, .[.and antigenically related variants thereof.]. .Iadd.said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend.   
     
     
       6. A synthetic polypeptide .[.having.]. .Iadd.that consists essentially of up to about 20 residues and includes .Iaddend.an amino acid residue sequence, taken from left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:   .[.H-.]. Gly-Gly-Gly-Ala-Gly-Gly-Ala-Gly-Ala-Gly-Gly-Gly-Ala-Gly-Gly-Ala-Gly.[.-OH.].;     .Iadd.and .Iaddend.the pharmaceutically acceptable salts thereof, .[.and antigenically related variants thereof.]. .Iadd.said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend.   
     
     
       7. A synthetic polypeptide .[.having.]. .Iadd.that consists essentially of up to about 20 residues and includes .Iaddend.an amino acid residue sequence, taken from left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:   .[.H-.]. Gly-Gly-Ala-Gly-Gly-Ala-Gly-Gly-Ala-Gly-Ala-Gly-Gly-Ala-Gly.[.-OH.].;     .Iadd.and .Iaddend.the pharmaceutically acceptable salts thereof, .[.and antigenically related variants thereof.]. .Iadd.said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend.   
     
     
       8. A synthetic polypeptide .[.having.]. .Iadd.that consists essentially of up to about 20 residues and includes .Iaddend.an amino acid residue sequence, taken from left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:   .[.H-.]. Gly-Gly-Ala-Gly-Ala-Gly-Gly-Ala-Gly-Ala-Gly-Gly-Ala-Gly-Ala-Gly-Gly-Ala-Gly-Ala-Gly- .[.-OH.].;     .Iadd.and .Iaddend.the pharmaceutically acceptable salts thereof, .[.and antigenically related variants thereof.]. .Iadd.said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend.   
     
     
       9. A synthetic polypeptide .[.having.]. .Iadd.that consists essentially of up to about 20 residues and includes .Iaddend.an amino acid residue sequence, taken from left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:   .[.H-.]. Gly-Ala-Gly-Gly-Ala-Gly-Ala-Gly-Gly-Gly-Ala-Gly-Gly-Ala-Gly-Gly.[.-OH.].;     .Iadd.and .Iaddend.the pharmaceutically acceptable salts thereof, .[.and antigenically related variants thereof.]. .Iadd.said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend.   
     
     
       10. A synthetic polypeptide .[.having.]. .Iadd.that consists essentially of up to about 20 residues and includes .Iaddend.an amino acid residue sequence, taken from the left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:   .[.H-.]. Gly-Gly-Gly-Ala-Gly-Gly-Ala-Gly-Ala-Gly-Gly-Gly-Ala-.Iadd.Gly.Iaddend.-Gly-Ala-Gly.[.-OH.].;     .Iadd.and .Iaddend.the pharmaceutically acceptable salts thereof, .[.and antigenically related variants thereof.]. .Iadd.said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend.   
     
     
       11. A synthetic polypeptide .[.having.]. .Iadd.that consists essentially of up to about 20 residues and includes .Iaddend.an amino acid residue sequence, taken from left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:   .[.H-.]. Ala-Gly-Gly-Ala-Gly-Ala-Gly-Gly-Gly-Ala-Gly-.Iadd.Gly.Iaddend.-Ala-Gly.[.-OH.].;     .Iadd.and .Iaddend.the pharmaceutically acceptable salts thereof, .[.and antigenically related variants thereof.]. .Iadd.said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend. .Iadd.12. A synthetic polypeptide that consists essentially of up to about 20 residues and includes an amino acid residue sequence, taken from left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:     Ala-Gly-Ala-Gly-Gly-Gly-Ala-Gly-Gly-Ala-Gly-Ala-Gly-Gly-Gly-Ala-Gly-Gly-Ala-Gly;     and the pharmaceutically acceptable salts thereof, said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend. .Iadd.13. A synthetic polypeptide that consists essentially of up to about 20 residues and includes an amino acid residue sequence, taken from left to right and in the direction of amino-terminus to carboxy-terminus, represented by the formula:     Gly-Gly-Ala-Gly-Gly-Ala-Gly-Gly-Ala-Gly-Ala-Gly-Gly-Gly-Ala-Gly; and     the pharmaceutically acceptable salts thereof, said polypeptide when linked to a carrier and used to immunize a rabbit, induces in said rabbit antibodies which bind specifically to Epstein-Barr virus nuclear antigen. .Iaddend.