Abstract
We used T cell-antigen-presenting cell (APC) combinations from two pairs of recombinant mouse strains, B10.A(4R)-B10.A(2R) and B10.S(7R)- B10.S(9R) (abbreviated 4R, 2R, 7R, 9R, respectively), which differ from each other only in the nonexpression vs. expression of cell-surface E molecules, to study the mechanism of the Ir gene-controlled (E- restricted) response to the terpolymer poly(glu51lys34tyr15) (GLT). No response to GLT occurred when the APC were from E-nonexpressor strains 4R and 7R. When APC from E-expressor strains were used and alloreactivity against the incompatible E molecules was removed by BUdR + light treatment, 7R T cells responded to GLT presented by 9R APC, but 4R T cells failed to respond to GLT presented by 2R APC. However, 4R T cells mounted a proliferative response to GLT presented by fully allogeneic 5R or 9R APC. The latter response was completely abolished by the depletion of cells alloreactive against 2R and 5R or 2R and 9R. Since removal of alloreactivity against 5R plus 9R did not affect the response of 4R T cells to GLT presented by either 5R or 9R cells, we conclude that the 4R T cells generated in response to GLT cross-react with the additional incompatibility presented by 2R cells, that is, the Ek beta chain. In contrast, 7R T cells recognizing GLT presented by 9R APC do not cross-react with Ek beta. These results demonstrate that "blind spots" in the T cell repertoire produced by depletion of cells alloreactive against a single chain of a class II MHC molecule can render a strain nonresponsive to a synthetic polypeptide antigen, and that this nonresponsiveness corresponds to that attributed to the MHC- linked Ir genes.
Full Text
The Full Text of this article is available as a PDF (595.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Clark R. B., Shevach E. M. Generation of T cell colonies from responder strain 2 guinea pigs that recognize the copolymer L-glutamic acid, L-lysine in association with nonresponder strain 13 Ia antigens. J Exp Med. 1982 Feb 1;155(2):635–640. doi: 10.1084/jem.155.2.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ishii N., Baxevanis C. N., Nagy Z. A., Klein J. Responder T cells depleted of alloreactive cells react to antigen presented on allogeneic macrophages from nonresponder strains. J Exp Med. 1981 Sep 1;154(3):978–982. doi: 10.1084/jem.154.3.978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ishii N., Baxevanis C. N., Nagy Z. A., Klein J. Selection of H-2 molecules for the context of antigen recognition by T lymphocytes. Immunogenetics. 1981;14(3-4):283–292. doi: 10.1007/BF00342197. [DOI] [PubMed] [Google Scholar]
- Ishii N., Nagy Z. A., Klein J. Absence of Ir gene control of T cells recognizing foreign antigen in the context of allogenic MHC molecules. Nature. 1982 Feb 11;295(5849):531–533. doi: 10.1038/295531a0. [DOI] [PubMed] [Google Scholar]
- Ishii N., Nagy Z. A., Klein J. Restriction molecules involved in the interaction of T cells with allogeneic antigen-presenting cells. J Exp Med. 1982 Aug 1;156(2):622–627. doi: 10.1084/jem.156.2.622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones P. P., Murphy D. B., McDevitt H. O. Two-gene control of the expression of a murine Ia antigen. J Exp Med. 1978 Oct 1;148(4):925–939. doi: 10.1084/jem.148.4.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones P. P., Murphy D. B., McDevitt H. O. Variable synthesis and expression of E alpha and Ae (E beta) Ia polypeptide chains in mice of different H-2 haplotypes. Immunogenetics. 1981;12(3-4):321–337. doi: 10.1007/BF01561674. [DOI] [PubMed] [Google Scholar]
- Lemke H., Hämmerling G. J., Hämmerling U. Fine specificity analysis with monoclonal antibodies of antigens controlled by the major histocompatibility complex and by the Qa/TL region in mice. Immunol Rev. 1979;47:175–206. doi: 10.1111/j.1600-065x.1979.tb00293.x. [DOI] [PubMed] [Google Scholar]
- Nagy Z. A., Baxevanis C. N., Ishii N., Klein J. Ia antigens as restriction molecules in Ir-gene controlled T-cell proliferation. Immunol Rev. 1981;60:59–83. doi: 10.1111/j.1600-065x.1981.tb00362.x. [DOI] [PubMed] [Google Scholar]
- Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
- Schwartz R. H. A clonal deletion model for Ir gene control of the immune response. Scand J Immunol. 1978;7(1):3–10. doi: 10.1111/j.1365-3083.1978.tb00420.x. [DOI] [PubMed] [Google Scholar]
- Schwartz R. H., Merryman C. F., Maurer P. H. Gene complementation in the T lymphocyte proliferative response to poly (Glu57Lys38Tyr5): evidence for effects of polymer handling and gene dosage. J Immunol. 1979 Jul;123(1):272–278. [PubMed] [Google Scholar]
- Singh S. K., Wakeland E. K., Vucak I., Nagy Z. A., Klein J. An H-2 haplotype possibly derived by crossing-over between (A alpha A beta) duplex and the E beta locus. Immunogenetics. 1981;14(3-4):273–281. doi: 10.1007/BF00342196. [DOI] [PubMed] [Google Scholar]
- Thomas D. W., Shevach E. M. Nature of the antigenic complex recognized by T lymphocytes: specific sensitization by antigens associated with allogeneic macrophages. Proc Natl Acad Sci U S A. 1977 May;74(5):2104–2108. doi: 10.1073/pnas.74.5.2104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Boehmer H., Haas W., Jerne N. K. Major histocompatibility complex-linked immune-responsiveness is acquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice. Proc Natl Acad Sci U S A. 1978 May;75(5):2439–2442. doi: 10.1073/pnas.75.5.2439. [DOI] [PMC free article] [PubMed] [Google Scholar]