Abstract
In vitro recombination of cloned H-2 genes resulted in two allogeneically novel mouse transplantation antigens in which the C2 domains of H-2Ld and H-2Dd were exchanged. These genes were introduced into mouse L cells by DNA-mediated gene transfer. We have used these transformed fibroblast lines, expressing recombinant H-2 antigens at normal levels, as targets for alloreactive cytotoxic T lymphocytes (CTL). Transformed cell lines expressing native or hybrid H-2 molecules that share the N and C1 domains but not the C2 domain were lysed to an equivalent degree by primary and secondary anti-H-2Dd CTL. Hybrid and native H-2 antigens that have the same N and C1 domains were capable of reciprocally blocking specific lysis by the CTL. Thus, polymorphic determinants recognized by alloreactive T cells are located primarily in the N domain, the C1 domain, or both domains of the H-2 antigen. In contrast, determinants recognized by monoclonal antibodies are present throughout the H-2 protein, including the C2 domain. Antibodies that bind specifically to the C2 domain effectively inhibited CTL activity, possibly due to steric effects. The same antibodies do not competitively inhibit the binding of N/C1-specific antibodies. The predominant reactivity of CTL to the N and C1 domains suggests that humoral and cellular responses "see" a different spectrum of alloantigenic determinants.
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Selected References
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- Epstein S. L., Ozato K., Sachs D. H. Blocking of allogeneic cell-mediated lympholysis by monoclonal antibodies to H-2 antigens. J Immunol. 1980 Jul;125(1):129–135. [PubMed] [Google Scholar]
- Evans G. A., Margulies D. H., Camerini-Otero R. D., Ozato K., Seidman J. G. Structure and expression of a mouse major histocompatibility antigen gene, H-2Ld. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1994–1998. doi: 10.1073/pnas.79.6.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Evans G. A., Margulies D. H., Shykind B., Seidman J. G., Ozato K. Exon shuffling: mapping polymorphic determinants on hybrid mouse transplantation antigens. Nature. 1982 Dec 23;300(5894):755–757. doi: 10.1038/300755a0. [DOI] [PubMed] [Google Scholar]
- Fathman C. G., Hengartner H. Clones of alloreactive T cells. Nature. 1978 Apr 13;272(5654):617–618. doi: 10.1038/272617a0. [DOI] [PubMed] [Google Scholar]
- MacDonald H. R., Cerottini J. C., Ryser J. E., Maryanski J. L., Taswell C., Widmer M. B., Brunner K. T. Quantitation and cloning of cytolytic T lymphocytes and their precursors. Immunol Rev. 1980;51:93–123. doi: 10.1111/j.1600-065x.1980.tb00318.x. [DOI] [PubMed] [Google Scholar]
- Margulies D. H., Evans G. A., Ozato K., Camerini-Otero R. D., Tanaka K., Appella E., Seidman J. G. Expression of H-2Dd and H-2Ld mouse major histocompatibility antigen genes in L cells after DNA-mediated gene transfer. J Immunol. 1983 Jan;130(1):463–470. [PubMed] [Google Scholar]
- Mellor A. L., Golden L., Weiss E., Bullman H., Hurst J., Simpson E., James R. F., Townsend A. R., Taylor P. M., Schmidt W. Expression of murine H-2Kb histocompatibility antigen in cells transformed with cloned H-2 genes. Nature. 1982 Aug 5;298(5874):529–534. doi: 10.1038/298529a0. [DOI] [PubMed] [Google Scholar]
- Moore K. W., Sher B. T., Sun Y. H., Eakle K. A., Hood L. DNA sequence of a gene encoding a BALB/c mouse Ld transplantation antigen. Science. 1982 Feb 5;215(4533):679–682. doi: 10.1126/science.7058332. [DOI] [PubMed] [Google Scholar]
- Nabholz M., Engers H. D., Collavo D., North M. Cloned T-cell lines with specific cytolytic activity. Curr Top Microbiol Immunol. 1978;81:176–187. doi: 10.1007/978-3-642-67448-8_29. [DOI] [PubMed] [Google Scholar]
- Nairn R., Yamaga K., Nathenson S. G. Biochemistry of the gene products from murine MHC mutants. Annu Rev Genet. 1980;14:241–277. doi: 10.1146/annurev.ge.14.120180.001325. [DOI] [PubMed] [Google Scholar]
- Ozato K., Hansen T. H., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. II. Antibodies to the H-2Ld antigen, the products of a third polymorphic locus of the mouse major histocompatibility complex. J Immunol. 1980 Dec;125(6):2473–2477. [PubMed] [Google Scholar]
- Ozato K., Mayer N. M., Sachs D. H. Monoclonal antibodies to mouse major histocompatibility complex antigens. Transplantation. 1982 Sep;34(3):113–120. doi: 10.1097/00007890-198209000-00001. [DOI] [PubMed] [Google Scholar]
- Ozato K., Mayer N., Sachs D. H. Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J Immunol. 1980 Feb;124(2):533–540. [PubMed] [Google Scholar]
- Potter T. A., Hansen T. H., Habbersett R., Ozato K., Ahmed A. Flow microfluorometric analysis of H-2L expression. J Immunol. 1981 Aug;127(2):580–584. [PubMed] [Google Scholar]
- Sherman L. A. Influence of the major histocompatibility complex on the repertoire of allospecific cytolytic T lymphocytes. J Exp Med. 1982 Feb 1;155(2):380–389. doi: 10.1084/jem.155.2.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sherman L. A. Recognition of conformational determinants on H-2 by cytolytic T lymphocytes. Nature. 1982 Jun 10;297(5866):511–513. doi: 10.1038/297511a0. [DOI] [PubMed] [Google Scholar]
- Weyand C., Goronzy J., Hämmerling G. J. Recognition of polymorphic H-2 domains by T lymphocytes. I. Functional role of different H-2 domains for the generation of alloreactive cytotoxic T lymphocytes and determination of precursor frequencies. J Exp Med. 1981 Dec 1;154(6):1717–1731. doi: 10.1084/jem.154.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
