Abstract
We report the first demonstration of Thy-1+, Lyt-2-, L3T4- MHC-specific CTL clones derived from the Lyt-2-, L3T4- subset of lymph node cells of C3H-gld/gld mice. These clones express alpha/beta heterodimeric TCRs on the cell surface and specifically recognize class I molecules on target cells. Lyt-2 and L3T4 molecules are therefore not essential for the induction, recognition, and killing of antigen-specific CTL. In addition, these studies suggest that antigen specificity development for class I structures may occur before Lyt-2 gene activation in the differentiation of T cells.
Full Text
The Full Text of this article is available as a PDF (1.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bank I., Chess L. Perturbation of the T4 molecule transmits a negative signal to T cells. J Exp Med. 1985 Oct 1;162(4):1294–1303. doi: 10.1084/jem.162.4.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Biddison W. E., Rao P. E., Talle M. A., Goldstein G., Shaw S. Possible involvement of the OKT4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of cytotoxic T lymphocytes specific for SB antigens. J Exp Med. 1982 Oct 1;156(4):1065–1076. doi: 10.1084/jem.156.4.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bier E., Hashimoto Y., Greene M. I., Maxam A. M. Active T-cell receptor genes have intron deoxyribonuclease hypersensitive sites. Science. 1985 Aug 9;229(4713):528–534. doi: 10.1126/science.3927483. [DOI] [PubMed] [Google Scholar]
- Borst J., van de Griend R. J., van Oostveen J. W., Ang S. L., Melief C. J., Seidman J. G., Bolhuis R. L. A T-cell receptor gamma/CD3 complex found on cloned functional lymphocytes. Nature. 1987 Feb 19;325(6106):683–688. doi: 10.1038/325683a0. [DOI] [PubMed] [Google Scholar]
- Brenner M. B., McLean J., Dialynas D. P., Strominger J. L., Smith J. A., Owen F. L., Seidman J. G., Ip S., Rosen F., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
- Brenner M. B., McLean J., Scheft H., Riberdy J., Ang S. L., Seidman J. G., Devlin P., Krangel M. S. Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes. Nature. 1987 Feb 19;325(6106):689–694. doi: 10.1038/325689a0. [DOI] [PubMed] [Google Scholar]
- Budd R. C., Cerottini J. C., MacDonald H. R. Cultured Lyt-2- L3T4- T lymphocytes from normal thymus or lpr mice express a broad spectrum of cytolytic activity. J Immunol. 1986 Dec 15;137(12):3734–3741. [PubMed] [Google Scholar]
- Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark S. P., Yoshikai Y., Taylor S., Siu G., Hood L., Mak T. W. Identification of a diversity segment of human T-cell receptor beta-chain, and comparison with the analogous murine element. 1984 Sep 27-Oct 3Nature. 311(5984):387–389. doi: 10.1038/311387a0. [DOI] [PubMed] [Google Scholar]
- Davidson W. F., Dumont F. J., Bedigian H. G., Fowlkes B. J., Morse H. C., 3rd Phenotypic, functional, and molecular genetic comparisons of the abnormal lymphoid cells of C3H-lpr/lpr and C3H-gld/gld mice. J Immunol. 1986 Jun 1;136(11):4075–4084. [PubMed] [Google Scholar]
- Davignon J. L., Budd R. C., Ceredig R., Piguet P. F., MacDonald H. R., Cerottini J. C., Vassalli P., Izui S. Functional analysis of T cell subsets from mice bearing the lpr gene. J Immunol. 1985 Oct;135(4):2423–2428. [PubMed] [Google Scholar]
- Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
- Engleman E. G., Benike C. J., Glickman E., Evans R. L. Antibodies to membrane structures that distinguish suppressor/cytotoxic and helper T lymphocyte subpopulations block the mixed leukocyte reaction in man. J Exp Med. 1981 Jul 1;154(1):193–198. doi: 10.1084/jem.154.1.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Fowlkes B. J., Edison L., Mathieson B. J., Chused T. M. Early T lymphocytes. Differentiation in vivo of adult intrathymic precursor cells. J Exp Med. 1985 Sep 1;162(3):802–822. doi: 10.1084/jem.162.3.802. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giorgi J. V., Zawadzki J. A., Warner N. L. Cytotoxic T lymphocyte lines reactive against murine plasmacytoma antigens: dissociation of cytotoxicity and Lyt-2 expression. Eur J Immunol. 1982 Oct;12(10):831–837. doi: 10.1002/eji.1830121007. [DOI] [PubMed] [Google Scholar]
- Golding H., Mizuochi T., McCarthy S. A., Cleveland C. A., Singer A. Relationship among function, phenotype, and specificity in primary allospecific T cell populations: identification of phenotypically identical but functionally distinct primary T cell subsets that differ in their recognition of MHC class I and class II allodeterminants. J Immunol. 1987 Jan 1;138(1):10–17. [PubMed] [Google Scholar]
- Hashimoto Y., Maxam A. M., Greene M. I. T-cell antigen-receptor genes in autoimmune mice. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7865–7869. doi: 10.1073/pnas.83.20.7865. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haskins K., Hannum C., White J., Roehm N., Kubo R., Kappler J., Marrack P. The antigen-specific, major histocompatibility complex-restricted receptor on T cells. VI. An antibody to a receptor allotype. J Exp Med. 1984 Aug 1;160(2):452–471. doi: 10.1084/jem.160.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krensky A. M., Clayberger C., Reiss C. S., Strominger J. L., Burakoff S. J. Specificity of OKT4+ cytotoxic T lymphocyte clones. J Immunol. 1982 Nov;129(5):2001–2003. [PubMed] [Google Scholar]
- Kung P., Goldstein G., Reinherz E. L., Schlossman S. F. Monoclonal antibodies defining distinctive human T cell surface antigens. Science. 1979 Oct 19;206(4416):347–349. doi: 10.1126/science.314668. [DOI] [PubMed] [Google Scholar]
- Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
- Lew A. M., Pardoll D. M., Maloy W. L., Fowlkes B. J., Kruisbeek A., Cheng S. F., Germain R. N., Bluestone J. A., Schwartz R. H., Coligan J. E. Characterization of T cell receptor gamma chain expression in a subset of murine thymocytes. Science. 1986 Dec 12;234(4782):1401–1405. doi: 10.1126/science.3787252. [DOI] [PubMed] [Google Scholar]
- Littman D. R., Gettner S. N. Unusual intron in the immunoglobulin domain of the newly isolated murine CD4 (L3T4) gene. 1987 Jan 29-Feb 4Nature. 325(6103):453–455. doi: 10.1038/325453a0. [DOI] [PubMed] [Google Scholar]
- MacDonald H. R., Glasebrook A. L., Cerottini J. C. Clonal heterogeneity in the functional requirement for Lyt-2/3 molecules on cytolytic T lymphocytes: analysis by antibody blocking and selective trypsinization. J Exp Med. 1982 Dec 1;156(6):1711–1722. doi: 10.1084/jem.156.6.1711. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maniatis T., Jeffrey A., Kleid D. G. Nucleotide sequence of the rightward operator of phage lambda. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1184–1188. doi: 10.1073/pnas.72.3.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marrack P., Endres R., Shimonkevitz R., Zlotnik A., Dialynas D., Fitch F., Kappler J. The major histocompatibility complex-restricted antigen receptor on T cells. II. Role of the L3T4 product. J Exp Med. 1983 Oct 1;158(4):1077–1091. doi: 10.1084/jem.158.4.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marshak-Rothstein A., Fink P., Gridley T., Raulet D. H., Bevan M. J., Gefter M. L. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. J Immunol. 1979 Jun;122(6):2491–2497. [PubMed] [Google Scholar]
- Mathieson B. J., Fowlkes B. J. Cell surface antigen expression on thymocytes: development and phenotypic differentiation of intrathymic subsets. Immunol Rev. 1984 Dec;82:141–173. doi: 10.1111/j.1600-065x.1984.tb01121.x. [DOI] [PubMed] [Google Scholar]
- Meuer S. C., Schlossman S. F., Reinherz E. L. Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4395–4399. doi: 10.1073/pnas.79.14.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moingeon P., Jitsukawa S., Faure F., Troalen F., Triebel F., Graziani M., Forestier F., Bellet D., Bohuon C., Hercend T. A gamma-chain complex forms a functional receptor on cloned human lymphocytes with natural killer-like activity. Nature. 1987 Feb 19;325(6106):723–726. doi: 10.1038/325723a0. [DOI] [PubMed] [Google Scholar]
- Ortega G., Robb R. J., Shevach E. M., Malek T. R. The murine IL 2 receptor. I. Monoclonal antibodies that define distinct functional epitopes on activated T cells and react with activated B cells. J Immunol. 1984 Oct;133(4):1970–1975. [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]
- Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
- Pierres A., Naquet P., Van Agthoven A., Bekkhoucha F., Denizot F., Mishal Z., Schmitt-Verhulst A. M., Pierres M. A rat anti-mouse T4 monoclonal antibody (H129.19) inhibits the proliferation of Ia-reactive T cell clones and delineates two phenotypically distinct (T4+, Lyt-2,3-, and T4-, Lyt-2,3+) subsets among anti-Ia cytolytic T cell clones. J Immunol. 1984 Jun;132(6):2775–2782. [PubMed] [Google Scholar]
- Reilly E. B., Kranz D. M., Tonegawa S., Eisen H. N. A functional gamma gene formed from known gamma-gene segments is not necessary for antigen-specific responses of murine cytotoxic T lymphocytes. 1986 Jun 26-Jul 2Nature. 321(6073):878–880. doi: 10.1038/321878a0. [DOI] [PubMed] [Google Scholar]
- Roths J. B., Murphy E. D., Eicher E. M. A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice. J Exp Med. 1984 Jan 1;159(1):1–20. doi: 10.1084/jem.159.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rupp F., Frech G., Hengartner H., Zinkernagel R. M., Joho R. No functional gamma-chain transcripts detected in an alloreactive cytotoxic T-cell clone. 1986 Jun 26-Jul 2Nature. 321(6073):876–878. doi: 10.1038/321876a0. [DOI] [PubMed] [Google Scholar]
- Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. 1984 Jun 28-Jul 4Nature. 309(5971):757–762. doi: 10.1038/309757a0. [DOI] [PubMed] [Google Scholar]
- Samelson L. E., Davidson W. F., Morse H. C., 3rd, Klausner R. D. Abnormal tyrosine phosphorylation on T-cell receptor in lymphoproliferative disorders. Nature. 1986 Dec 18;324(6098):674–676. doi: 10.1038/324674a0. [DOI] [PubMed] [Google Scholar]
- Samelson L. E., Lindsten T., Fowlkes B. J., van den Elsen P., Terhorst C., Davis M. M., Germain R. N., Schwartz R. H. Expression of genes of the T-cell antigen receptor complex in precursor thymocytes. 1985 Jun 27-Jul 3Nature. 315(6022):765–768. doi: 10.1038/315765a0. [DOI] [PubMed] [Google Scholar]
- Shinohara N., Kojima M. Mouse alloantibodies capable of blocking cytotoxic T cell function. V. The majority of I region-specific CTL are Lyt-2+ but are relatively resistant to anti-Lyt-2 blocking. J Immunol. 1984 Feb;132(2):578–583. [PubMed] [Google Scholar]
- Siu G., Kronenberg M., Strauss E., Haars R., Mak T. W., Hood L. The structure, rearrangement and expression of D beta gene segments of the murine T-cell antigen receptor. 1984 Sep 27-Oct 3Nature. 311(5984):344–350. doi: 10.1038/311344a0. [DOI] [PubMed] [Google Scholar]
- Staerz U. D., Rammensee H. G., Benedetto J. D., Bevan M. J. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. J Immunol. 1985 Jun;134(6):3994–4000. [PubMed] [Google Scholar]
- Swain S. L. Significance of Lyt phenotypes: Lyt2 antibodies block activities of T cells that recognize class 1 major histocompatibility complex antigens regardless of their function. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7101–7105. doi: 10.1073/pnas.78.11.7101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swain S. L. T cell subsets and the recognition of MHC class. Immunol Rev. 1983;74:129–142. doi: 10.1111/j.1600-065x.1983.tb01087.x. [DOI] [PubMed] [Google Scholar]
- Wassmer P., Chan C., Lögdberg L., Shevach E. M. Role of the L3T4-antigen in T cell activation. II. Inhibition of T cell activation by monoclonal anti-L3T4 antibodies in the absence of accessory cells. J Immunol. 1985 Oct;135(4):2237–2242. [PubMed] [Google Scholar]
- Wilde D. B., Marrack P., Kappler J., Dialynas D. P., Fitch F. W. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed] [Google Scholar]
- Zamoyska R., Vollmer A. C., Sizer K. C., Liaw C. W., Parnes J. R. Two Lyt-2 polypeptides arise from a single gene by alternative splicing patterns of mRNA. Cell. 1985 Nov;43(1):153–163. doi: 10.1016/0092-8674(85)90020-0. [DOI] [PubMed] [Google Scholar]
- van den Elsen P., Shepley B. A., Borst J., Coligan J. E., Markham A. F., Orkin S., Terhorst C. Isolation of cDNA clones encoding the 20K T3 glycoprotein of human T-cell receptor complex. 1984 Nov 29-Dec 5Nature. 312(5993):413–418. doi: 10.1038/312413a0. [DOI] [PubMed] [Google Scholar]