Delineation of several DR-restricted tetanus toxin T cell epitopes.

We have characterized five human T cell clones specific for tetanus toxin. The combination of different techniques allowed us to precisely map two T cell epitopes within fragments 830-843 and 1273-1284 of tetanus toxin, as formally demonstrated by the use of corresponding synthetic peptides. The three other T cell clones were specific for regions 2-602, 604-742, and 865-1315 of tetanus toxin, respectively. The five T cell clones were shown to be restricted to HLA-DR Ag. Furthermore, the allele of HLA-DR utilized by the various epitopes has been determined. The use of HLA-DR-transfected L cells as APC directly demonstrated that two epitopes, one of which represented by fragment 1273-1284, were recognized in association with HLA-DRw52a. For the other three T cell epitopes, the data strongly suggested they were recognized in association with HLA-DR5. Finally, a sixth T cell clone was shown to be specific for tetanus toxoid, the vaccinal preparation of tetanus toxin, and not for other tetanus toxin fragments. This indicated that immunization with tetanus toxoid probably elicits a T cell response directed only in part against native tetanus toxin.

[1]  B. Mach,et al.  Functional polymorphism of each of the two HLA-DR beta chain loci demonstrated with antigen-specific DR3- and DRw52-restricted T cell clones , 1988, The Journal of experimental medicine.

[2]  H. Margalit,et al.  Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein. , 1987, Science.

[3]  A. Henschen,et al.  Tetanus toxin: primary structure, expression in E. coli, and homology with botulinum toxins. , 1986, The EMBO journal.

[4]  E. Unanue,et al.  Binding of immunogenic peptides to Ia histocompatibility molecules , 1985, Nature.

[5]  R. Hodges,et al.  T cell autoreactivity to insulin in diabetic and related non-diabetic individuals. , 1988, Journal of Immunology.

[6]  G. Drapeau,et al.  Staphylococcal protease: a proteolytic enzyme specific for glutamoyl bonds. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[7]  L. Otvos,et al.  Recognition of hepatitis B surface antigen by human T lymphocytes. Proliferative and cytotoxic responses to a major antigenic determinant defined by synthetic peptides. , 1988, Journal of immunology.

[8]  R. Young,et al.  Mapping of T cell epitopes using recombinant antigens and synthetic peptides. , 1987, The EMBO journal.

[9]  C. Hirs [19] Performic acid oxidation☆ , 1967 .

[10]  H. Grey,et al.  Antigen recognition by H-2-restricted T cells. II. A tryptic ovalbumin peptide that substitutes for processed antigen. , 1984, Journal of immunology.

[11]  M. A. Saper,et al.  The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens , 1987, Nature.

[12]  J. Freed,et al.  Interaction between a "processed" ovalbumin peptide and Ia molecules. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. H. Brown A hypothetical model of the foreign antigen binding site of Class II histocompatibility molecules , 1988, Nature.

[14]  A. Lanzavecchia,et al.  Mapping of T Cell Epitopes in Proteins: A Chemical Approach , 1990 .

[15]  B. McGinn,et al.  Non-responsiveness to a foot-and-mouth disease virus peptide overcome by addition of foreign helper T-cell determinants , 1987, Nature.

[16]  B. Mach,et al.  FUNCTIONAL POLYMORPHISM OF EACH OF THE TWO HLA-DR a CHAIN LOCI DEMONSTRATED WITH , 1988 .

[17]  Antonio Lanzavecchia,et al.  Antigen-specific interaction between T and B cells , 1985, Nature.

[18]  Leonore A. Herzenberg,et al.  Carrier-priming leads to hapten-specific suppression , 1980, Nature.

[19]  N. H. Wellhöner Tetanus neurotoxin. , 1982, Reviews of physiology, biochemistry and pharmacology.

[20]  A. Proudfoot,et al.  Multiple T cell antigenic determinants identified within a limited region of the horse cytochrome c molecule , 1987, European journal of immunology.

[21]  G. B. Thornton,et al.  Antibody production to the nucleocapsid and envelope of the hepatitis B virus primed by a single synthetic T cell site , 1987, Nature.

[22]  H. Grey,et al.  Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing , 1983, The Journal of experimental medicine.

[23]  C. Leclerc,et al.  A synthetic vaccine constructed by copolymerization of B and T cell determinants , 1987, European journal of immunology.

[24]  E. Unanue,et al.  Processing of lysozyme by macrophages: identification of the determinant recognized by two T-cell hybridomas. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[25]  A. Moriarty,et al.  Hepatitis B synthetic immunogen comprised of nucleocapsid T-cell sites and an envelope B-cell epitope. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Eric O Long,et al.  Structural model of HLA-DR1 restricted T cell antigen recognition , 1988, Cell.

[27]  G. Corradin,et al.  Cleavage of cytochrome c with cyanogen bromide. , 1970, Biochimica et biophysica acta.