Abstract
Antibodies raised against many structurally related antigens have been shown to cross-react extensively. Manifestations of T-cell immunity, on the other hand, appear to be more restricted in their ability to be elicited by cross-reacting antigens, although examples have been reported. This paper explores the nature of the cross-reactions at the T-cell level among the branched-chain copolymers (T,G)-A--L, (phi,G)-A-- L, (H,G)-A--L, and G-A--L, as well as a related linear terpolymer, GAT, in a variety of mouse strains using the peritoneal exudate T-lymphocyte- enriched cells (PETLES) proliferation assay. (T,G)-A--L, (phi,G)-A--L, and GAT could cross-stimulate cells immune to the other two antigens, whereas (H,G)-A--L, (T,G)-Pro--L, and G-A--L showed no cross- stimulations. The extent of the cross-reactions varied with the mouse strain and was shown to be under the control of immune response genes. It was necessary for the strain to be able to respond to both the immunogen and the cross-reacting antigen, when used as an immunogen, in order for cross-stimulation to occur; however, this was not always sufficient. Several examples of unequal or one-way cross-reactions were found. In addition, the immune responses to (H,G)-A--L and (phi,G)-A--L showed no cross-reactions with the other antigen even though their Ir genes were both mapped to the K region or I-A subregion. The problem of accounting for such fine specificity of T-cell recognition in lieu of the genetic evidence demonstrating only Ir gene control of the response is discussed.
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- Benacerraf B., Katz D. H. The histocompatibility-linked immune response genes. Adv Cancer Res. 1975;21:121–173. doi: 10.1016/s0065-230x(08)60972-0. [DOI] [PubMed] [Google Scholar]
- Binz H., Wigzell H. Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. I. Demonstration of similar or identical idiotypes on IgG molecules and T-cell receptors with specificity for the same alloantigens. J Exp Med. 1975 Jul 1;142(1):197–211. doi: 10.1084/jem.142.1.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Click R. E., Benck L., Alter B. J. Immune responses in vitro. I. Culture conditions for antibody synthesis. Cell Immunol. 1972 Feb;3(2):264–276. doi: 10.1016/0008-8749(72)90165-7. [DOI] [PubMed] [Google Scholar]
- Dorf M. E., Benacerraf B. Complementation of H-2-linked Ir genes in the mouse. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3671–3675. doi: 10.1073/pnas.72.9.3671. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eichmann K., Rajewsky K. Induction of T and B cell immunity by anti-idiotypic antibody. Eur J Immunol. 1975 Oct;5(10):661–666. doi: 10.1002/eji.1830051002. [DOI] [PubMed] [Google Scholar]
- Fuchs S., Sela M. Antigenicity of some new synthetic polypeptides and polypeptidyl gelatins. Biochem J. 1964 Dec;93(3):566–572. doi: 10.1042/bj0930566. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hill S. W., Sercarz E. E. Fine specificity of the H-2 linked immune response gene for the gallinaceous lysozymes. Eur J Immunol. 1975 May;5(5):317–324. doi: 10.1002/eji.1830050506. [DOI] [PubMed] [Google Scholar]
- Janeway C. A., Cohen B. E., Ben-Sasson S. Z., Paul W. E. The specificity of cellular immune responses in guinea pigs. I. T cells specific for 2,4-dinitrophenyl-o-tyrosyl residues. J Exp Med. 1975 Jan 1;141(1):42–55. doi: 10.1084/jem.141.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaton J. C., Sela M. Role of optical configuration in the immunogenicity and specificity of synthetic antigens derived from multichain polyproline. J Biol Chem. 1968 Nov 10;243(21):5616–5626. [PubMed] [Google Scholar]
- KATCHALSKI E., SELA M. Synthesis and chemical properties of poly-alpha-amino acids. Adv Protein Chem. 1958;13:243–492. doi: 10.1016/s0065-3233(08)60600-2. [DOI] [PubMed] [Google Scholar]
- Lieberman R., Paul W. E., Humphrey W., Jr, Stimpfling J. H. H-2-linked immune response (Ir) genes. Independent loci for Ir-IgG and Ir-IgA genes. J Exp Med. 1972 Nov 1;136(5):1231–1240. doi: 10.1084/jem.136.5.1231. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lonai P., McDevitt H. O. Genetic control of the immune response: in vitro stimulation of lymphocytes by (T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L. J Exp Med. 1974 Oct 1;140(4):977–994. doi: 10.1084/jem.140.4.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McDevitt H. O., Chinitz A. Genetic control of the antibody response: relationship between immune response and histocompatibility (H-2) type. Science. 1969 Mar 14;163(3872):1207–1208. doi: 10.1126/science.163.3872.1207. [DOI] [PubMed] [Google Scholar]
- McDevitt H. O., Deak B. D., Shreffler D. C., Klein J., Stimpfling J. H., Snell G. D. Genetic control of the immune response. Mapping of the Ir-1 locus. J Exp Med. 1972 Jun 1;135(6):1259–1278. doi: 10.1084/jem.135.6.1259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McDevitt H. O., Sela M. Genetic control of the antibody response. II. Further analysis of the specificity of determinant-specific control, and genetic analysis of the response to (H,G)-A--L in CBA and C57 mice. J Exp Med. 1967 Nov 1;126(5):969–978. doi: 10.1084/jem.126.5.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Merryman C. F., Maurer P. H. Genetic control of immune response to glutamic acid, alanine, tyrosine copolymers in mice. I. Association of responsiveness to H-2 genotype and specificity of the response. J Immunol. 1972 Jan;108(1):135–141. [PubMed] [Google Scholar]
- Mozes E., Schwartz M., Sela M. Antibody response of inbred mouse strains to ordered tetrapeptides of tyrosine and glutamic acid attached to multichain polyalanine or polyproline. Tyr-Tyr-Glu-Glu is a major determinant of the random poly-(Tyr, Glu)-polyDLAla--polyLys. J Exp Med. 1974 Aug 1;140(2):349–355. doi: 10.1084/jem.140.2.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paul W. E. Functional specificity of antigen-binding receptors of lymphocytes. Transplant Rev. 1970;5:130–166. doi: 10.1111/j.1600-065x.1970.tb00359.x. [DOI] [PubMed] [Google Scholar]
- SELA M., FUCHS S., ARNON R. Studies on the chemical basis of the antigenicity of proteins. 5. Synthesis, characterization and immunogenicity of some multichain and linear polypeptides containing tyrosine. Biochem J. 1962 Oct;85:223–235. doi: 10.1042/bj0850223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schlossman S. F., Herman J., Yaron A. Antigen recognition: in vitro studies on the specificity of the cellular immune response. J Exp Med. 1969 Nov 1;130(5):1031–1045. doi: 10.1084/jem.130.5.1031. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz R. H., Jackson L., Paul W. E. T lymphocyte-enriched murine peritoneal exudate cells. I. A reliable assay for antigen-induced T lymphocyte proliferation. J Immunol. 1975 Nov;115(5):1330–1338. [PubMed] [Google Scholar]
- Schwartz R. H., Paul W. E. T-lymphocyte-enriched murine peritoneal exudate cells. II. Genetic control of antigen-induced T-lymphocyte proliferation. J Exp Med. 1976 Mar 1;143(3):529–540. doi: 10.1084/jem.143.3.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seaver S. S., Brown A., Hämmerling G., McDevitt H. O. Genetic control of the immune response: ability of antigens of defined amino acid sequence to be recognized by the Ir-1 gene system. Eur J Immunol. 1976 Jul;6(7):502–507. doi: 10.1002/eji.1830060711. [DOI] [PubMed] [Google Scholar]
- Taussig J., Mozes E., Isac R. Antigen-specific thymus cell factors in the genetic control of the immune response to poly-(tyrosyl, glutamyl)-poly-D, L-alanyl--poly-lysyl. J Exp Med. 1974 Aug 1;140(2):301–312. doi: 10.1084/jem.140.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson D. B., Nowell P. C. Quantitative studies on the mixed lymphocyte interaction in rats. V. Tempo and specificity of the proliferative response and the number of reactive cells from immunized donors. J Exp Med. 1971 Mar 1;133(3):442–453. doi: 10.1084/jem.133.3.442. [DOI] [PMC free article] [PubMed] [Google Scholar]