Abstract
We have examined the individual contributions of the I-A kappa alpha chain, the I-A kappa beta chain, and the foreign antigen hen egg-white lysozyme (HEL) in the formation of the determinant being recognized by the T cell receptor. As functional probes we have used (a) a panel of 10 HEL-specific T cell hybridomas, (b) a panel of antigen-presenting cells (APC) possessing mutations in either the I-A kappa alpha or I-A kappa beta chains, and (c) proteolytic fragment of HEL and related synthetic peptides. The ability of the I-A kappa beta and I-A kappa alpha mutant cell lines to present antigen to the 10 T cell hybridomas divided these T cells into six distinct groups. These HEL-specific T cells therefore appear to recognize several distinct domains on the I-A kappa molecule. The 10 T cell hybrids were then shown to recognize at least three distinct determinants on the HEL molecule, with 8 of the 10 hybrids recognizing one of two major determinants HEL(46-61) or HEL(34- 45). Combining the response patterns to the panel of I-A kappa mutant APC lines with the antigen specificity revealed that the 10 T cell hybrids recognized at least eight unique determinants formed by the I-A kappa alpha chains, I-A kappa beta chains, and HEL peptides. This analysis provides direct evidence that a large number of different determinants or T cell receptor ligands can be generated from a single Ia molecule and a simple globular protein.
Full Text
The Full Text of this article is available as a PDF (683.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allen P. M., Strydom D. J., Unanue E. R. Processing of lysozyme by macrophages: identification of the determinant recognized by two T-cell hybridomas. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2489–2493. doi: 10.1073/pnas.81.8.2489. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Atassi M. Z., Habeeb A. F., Ando K. Enzymic and immunochemical properties of lysozyme. VII. Location of all the antigenic reactive regions. A new approach to study immunochemistry of tight proteins. Biochim Biophys Acta. 1973 Mar 23;303(1):203–209. [PubMed] [Google Scholar]
- Beck B. N., Glimcher L. H., Nilson A. E., Pierres M., McKean D. J. The structure-function relationship of I-A molecules: correlation of serologic and functional phenotypes of four I-Ak mutant cell lines. J Immunol. 1984 Dec;133(6):3176–3182. [PubMed] [Google Scholar]
- Beck B. N., Nelson P. A., Fathman C. G. The I-Ab mutant B6.C-H-2bm12 allows definition of multiple T cell epitopes on I-A molecules. J Exp Med. 1983 May 1;157(5):1396–1404. doi: 10.1084/jem.157.5.1396. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Conrad P. J., Lerner E. A., Murphy D. B., Jones P. P., Janeway C. A., Jr Differential expression of Ia glycoprotein complexes in F1 hybrid mice detected with alloreactive cloned T cell lines. J Immunol. 1982 Dec;129(6):2616–2620. [PubMed] [Google Scholar]
- Fathman C. G., Kimoto M., Melvold R., David C. S. Reconstitution of Ir genes, Ia antigens, and mixed lymphocyte reaction determinants by gene complementation. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1853–1857. doi: 10.1073/pnas.78.3.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frelinger J. G., Shigeta M., Infante A. J., Nelson P. A., Pierres M., Fathman C. G. Multiple functional sites on a single Ia molecule defined using T cell clones and antibodies with chain-determined specificity. J Exp Med. 1984 Mar 1;159(3):704–715. doi: 10.1084/jem.159.3.704. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Glimcher L. H., Hamano T., Asofsky R., Sachs D. H., Pierres M., Samelson L. E., Sharrow S. O., Paul W. E. IA mutant functional antigen-presenting cell lines. J Immunol. 1983 May;130(5):2287–2294. [PubMed] [Google Scholar]
- Glimcher L. H., Sharrow S. O., Paul W. E. Serologic and functional characterization of a panel of antigen-presenting cell lines expressing mutant I-A class II molecules. J Exp Med. 1983 Nov 1;158(5):1573–1588. doi: 10.1084/jem.158.5.1573. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heber-Katz E., Hansburg D., Schwartz R. H. The Ia molecule of the antigen-presenting cell plays a critical role in immune response gene regulation of T cell activation. J Mol Cell Immunol. 1983;1(1):3–18. [PubMed] [Google Scholar]
- Heber-Katz E., Schwartz R. H., Matis L. A., Hannum C., Fairwell T., Appella E., Hansburg D. Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation. J Exp Med. 1982 Apr 1;155(4):1086–1099. doi: 10.1084/jem.155.4.1086. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hedrick S. M., Matis L. A., Hecht T. T., Samelson L. E., Longo D. L., Heber-Katz E., Schwartz R. H. The fine specificity of antigen and Ia determinant recognition by T cell hybridoma clones specific for pigeon cytochrome c. Cell. 1982 Aug;30(1):141–152. doi: 10.1016/0092-8674(82)90020-4. [DOI] [PubMed] [Google Scholar]
- Hochman P. S., Huber B. T. A class II gene conversion event defines an antigen-specific Ir gene epitope. J Exp Med. 1984 Dec 1;160(6):1925–1930. doi: 10.1084/jem.160.6.1925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hünig T. R., Bevan M. J. Antigen recognition by cloned cytotoxic T lymphocytes follows rules predicted by the altered-self hypothesis. J Exp Med. 1982 Jan 1;155(1):111–125. doi: 10.1084/jem.155.1.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenthal A. S., Shevach E. M. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med. 1973 Nov 1;138(5):1194–1212. doi: 10.1084/jem.138.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]