Abstract
L-Tyrosine azobenzene-p-arsonate (RAT) induced cellular immunity without antibody production in guinea pigs. Bifunctional antigens were prepared consisting of one RAT carrier moiety linked either directly to a dinitrophenyl (DNP) haptenic determinant or through one or more 6-amino-caproyl (SAC) spacers. Each SAC unit has an extended span of 8 A. Guinea pigs immunized with these conjugates developed cellular immunity directed against the RAT determinant and antibody specific for the DNP determinant. The anti-DNP response was the same with one or three SAC spacers, but was significantly weaker when the two determinants were joined without a spacer. Animals immunized with either DNP-SAC-TYR or DNP-TYR developed neither cellular nor humoral immunity. Prior immunization with RAT potentiated the secondary anti-hapten response to DNP-SAC-RAT. Modification of RAT at either the arsonate or tyrosine positions showed that other charged groups (sulfonate and trimethylammonium) could substitute for arsonate without loss of immunogenicity. Removal of either the amino or carboxyl group from the side chain of tyrosine did not abolish immunogenicity, but immunogenicity was lost upon removal of both. Immunization with symmetrical bifunctional RAT-(SAC)n-RAT and cyclo-(L-RAT-D-RAT) antigens led to cellular immunity but no anti-arsonate antibody, suggesting a barrier to "self-help." These compounds were also ineffective in inducing a secondary anti-arsonate response in animals primed with arsonate-BSA conjugates and RAT.
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Selected References
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- Alkan S. S., Nitecki D. E., Goodman J. W. Antigen recognition and the immune response: the capacity of L-tyrosine-azobenzenearsonate to serve as a carrier for a macromolecular hapten. J Immunol. 1971 Aug;107(2):353–358. [PubMed] [Google Scholar]
- Frey J. R., de Weck A. L., Geleick H., Lergier W. The immunogenicity of dinitrophenyl amino acids. J Exp Med. 1969 Nov 1;130(5):1123–1143. doi: 10.1084/jem.130.5.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goodman J. W., Nitecki D. E. Studies on the relation of a prior immune response to immunogenicity. Immunology. 1967 Dec;13(6):577–583. [PMC free article] [PubMed] [Google Scholar]
- Halpern B., Mitecki D. E. The deblocking of t-butyloxycarbonyl-peptides with formic acid. Tetrahedron Lett. 1967 Aug;31:3031–3033. doi: 10.1016/s0040-4039(00)90909-2. [DOI] [PubMed] [Google Scholar]
- Katz D. H., Paul W. E., Goidl E. A., Benacerraf B. Carrier function in anti-hapten immune responses. I. Enhancement of primary and secondary anti-hapten antibody responses by carrier preimmunization. J Exp Med. 1970 Aug 1;132(2):261–282. doi: 10.1084/jem.132.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leskowitz S., Jones V. E., Zak S. J. Immunochemical study of antigenic specificity in delayed hypersensitivity. V. Immunization with monovalent low molecular weight conjugates. J Exp Med. 1966 Feb 1;123(2):229–237. doi: 10.1084/jem.123.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leskowitz S., Zak S. J. Production of hapten-specific delayed sensitivity with low molecular weight conjugates. Nature. 1966 Jul 16;211(5046):246–248. doi: 10.1038/211246a0. [DOI] [PubMed] [Google Scholar]
- Marglin A., Merrifield R. B. Chemical synthesis of peptides and proteins. Annu Rev Biochem. 1970;39:841–866. doi: 10.1146/annurev.bi.39.070170.004205. [DOI] [PubMed] [Google Scholar]
- Rajewsky K., Schirrmacher V., Nase S., Jerne N. K. The requirement of more than one antigenic determinant for immunogenicity. J Exp Med. 1969 Jun 1;129(6):1131–1143. doi: 10.1084/jem.129.6.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Senyk G., Williams E. B., Nitecki D. E., Goodman J. W. The functional dissection of an antigen molecule: specificity of humoral and cellular immune responses to glucagon. J Exp Med. 1971 Jun 1;133(6):1294–1308. doi: 10.1084/jem.133.6.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shaltiel S. Thiolysis of some dinitrophenyl derivatives of amino acids. Biochem Biophys Res Commun. 1967 Oct 26;29(2):178–183. doi: 10.1016/0006-291x(67)90583-9. [DOI] [PubMed] [Google Scholar]
- TABACHNICK M., SOBOTKA H. Azoproteins. I. Spectrophotometric studies of amino acid azo derivatives. J Biol Chem. 1959 Jul;234(7):1726–1730. [PubMed] [Google Scholar]
- TABACHNICK M., SOBOTKA H. Azoproteins. II. A spectrophotometric study of the coupling of diazotized arsanilic acid with proteins. J Biol Chem. 1960 Apr;235:1051–1054. [PubMed] [Google Scholar]
