Abstract
Thymocyte differentiation and the subsequent production of peripheral functional T cells involve positive and negative selection events on developing thymocytes expressing a number of specific surface molecules, including the T cell receptor (TCR) and the coreceptor molecules CD4 and CDS. At least two different mechanisms may be responsible for the effects of CD4 and CDS on T cell development. CD4 binding to major histocompatibility complex (MHC) class II proteins1 and CDS binding to MHC class I proteins2 may increase the strength of interaction between the cells involved in the selection processes.3 Signal transduction through these coreceptors may also play an important role during thymocyte development. Recent evidence indicates that CD4 and CDS play important roles in signal transduction during T cell activation.4-9
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References
C. Doyle. and J.L. Strominger, Interaction between CD4 and class II MHC molecules mediates cell adhesion, Nature 330:56 (1987).
A. Norment, R.D. Salter, P. Parham, V.H. Englehard, and D.L. Littman, Cell-cell adhesion mediated by CD8 and MHC class I molecules, Nature 336:79 (1988).
R.H. Seong, C.H. Liaw, S. Michie, J.R Parnes, and J.W. Chamberlain, Effects of high level constitutive expression of transgenic CD8∝ on thymic selection, Submitted.
A. Veillette, A. Brookman, E.M. Horak, L.E. Samelson, and J.B. Bolen, Signal transduction through the CD4 receptor involves the activation of the internal membrane protein kinase p56lck, Nature 338:257 (1989).
A. Veillette, J.B. Bolen, and M.A. Brookman, Alteration in tyrosine phosphorylation induced by antibody-mediated cross-linking of CD4 receptor of T lymphocytes, Mol. Cell. Biol. 9:4441 (1989).
K. Luo and B.M. Sefton, Crosslinking of T cell surface molecules CD4 and CD8 stimulates phosphorylation of the lck tyrosine protein kinase at the autophosphorylation site, Mol. Cell. Biol. 10:5305 (1990).
R. Zamoyska, P. Durham, S.D. Gorman, P. von Hoegen, J.B. Bolen, A.V. Veillette, and J.R. Parnes, Inability of CD8∝’ polypeptide to associate with p56lck correlates with impaired function in vitro and lack of expression in vivo, Nature 342:278 (1989).
M.C. Miceli, P. von Hoegen, and J.R. Parnes, Coreceptor versus adhesion function of CD4 and CD8: role of the cytoplasmic tail in coreceptor activity, Proc. Natl. Acad. Sci. USA. 88:2623 (1991).
N. Glaichenhaus, N. Shastri, D.R. Littman, and J.M. Turner, Requirement for association of p561ck with CD4 in antigen-specific signal transduction in T cells, Cell 64:511 (1991).
H.-S. Teh, P. Kisielow, B. Scott, H. Kishi, H. Uematsu, Y. Bluthmann, and H. von Boehmer, Thymic major histocompatibility complex antigens and the alpha beta T-cell receptor determine the CD4/CD8 phenotype of T cells, Nature 335:229 (1988).
W.C. Sha, C.A. Nelson, R.D. Newberry, D.M. Kranz, J.H. Russel, and D.Y. Loh, Selective expression of an antigen receptor on CD8-bearing T lymphocytes in transgenic mice, Nature 335:271 (1988).
L.J. Berg, A.M. Pullen, B. Fazekas de St. Groth, D. Mathis, C. Benoist, and M.M. Davis, Antigen/MHC-specific T cells are preferentially exported from thymus in the presence of their MHC ligand, Cell 58:1035 (1989).
J. Kaye, M.-L. Hsu, M.-E. Sauron, S.C. Jameson, N.R. Gascoigne, and S.M. Hedrick, Selective development of CD4+ T cells in transgenic mice expressing class II MHC-restricted antigen receptor, Nature 341:746 (1989).
H. von Boehmer, P. Kisielow, H. Kishi, B. Scott, P. Borgulya, and H.-S. Teh, The expression of CD4 and CD8 accessory molecules on mature T cells is not random but correlates with the specificity of the ab receptor for antigen, Immunol. Rev. 109:144 (1989).
E.A. Robey, B.J. Fowlkes, and D.M. Pardoll, Molecular mechanisms for lineage commitment in T cell development, Semin. Immnol. 2:25 (1990).
E.A. Robey, B.J. Fowlkes, J.W. Gordon, D. Kioussis, H. von Bohmer, F. Ramsdell, and R. Axel, Thymic selection in CD8 transgenic mice supports an instructive model for commitment to a CD4 or CD8 lineage, Cell 64:99 (1991).
P. Borgulya, H. Kishi, U. Muller, J. Kirberg, and H. von Boehmer, Development of the CD4 and CD8 lineage of T cells: instruction versus selection, EMBO J. 10:913 (1991).
H.-S. Teh, H. Kishi, B. Scott, and H. von Bohmer, Deletion of autospecific T cells in T cell receptor (TCR) transgenic mice spares cells with normal TCR levels and low levels of CD8 molecules, J. Exp. Med. 169:795 (1989).
J.A. Ledbetter, W. Seaman, T. Tsu, and L. A. Herzenberg, Ly-2 and Ly-3 antigens are on two different polypeptide subunits linked by disulfide bonds, J. Exp. Med. 153:1503 (1981).
P. Gunning, J. Leavitt, G. Muscat, S. Ng, and L. Kedes, A human β-actin expression vector system directs high-level accumulation of antisense transcripts, Proc. Natl. Acad. Sci. 84:4831 (1987).
S.D. Gorman, B. Tourvieille, and J.R. Parnes, Structure of the mouse gene encoding CD4 and an unusual transcript in brain, Proc. Natl. Acad. Sci. U.S.A. 84:7644 (1987).
R.H. Seong, J.W. Chamberlain, and J.R. Parnes, CD4 transmembrane region and/or cytoplasmic tail delivers a specific signal for T cell differrentiation to a CD4 cell lineage, Nature In press.
P. Kisielow, H. Bluthman, U.D. Staerz, M. Steinmetz, and H. von Boehmer, Tolerence in T-cell-receptor transgenic mice involves deletion of nonmature CD4+C08+ thymocytes, Nature 333:742 (1988).
P. Kisielow, S.-H. Teh, H. Bluthman, and H. von Boehmer, Positive selection of antigen-specific T cells in thymus by restricting MHC molecules, Nature 335:730 (1988).
M.J. Bevan and P. Fink, The influence of thymus H-2 antigens on the specificity of maturing killer and helper cells, Immunol. Rev. 269:417 (1977).
R.H. Zinkernagel, G. Callahan, A. Althage, S. Cooper, P. Klein, and J. Klein, On the thymus in the differentiation of H-2 self-recognition by T cells: evidence for dual recognition? J. Exp. Med. 147:882 (1978).
H. von Boehmer, W. Haas, and N.K. Jerne, Major histocompatibilitycomplex-linked immune-responsiveness is aquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice, Proc. Natl. Acad. Sci. U.S.A. 75:2434 (1978).
J. Kappler and P.J. Marrack, The role of H-2 linked genes in helper T cell function IV. Importance of T-cell genetype and host environment in I region and Ir gene expression, J. Exp. Med. 148:1510 (1978).
C.E. Rudd, J.M. Trevillyan, J.D. Dasgupta, L.L. Wong, and S.F. Schlossman, The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (Pp58) from human T lymphocytes, Proc. Natl. Acad. Sci. U.S.A. 85:5190 (1988).
A. Veillete, M.A. Bookman, E.M. Horak, and J.B. Bolen, The CD4 and CD8 Tcell surface antigens are physically associated with the internal membrane tyrosine kinase p56lck, Cell 55:301 (1988).
A. Veillete, J.C. Zuniga-Pflucker, J.B. Bolen, and A.M. Kruisbeek, Engagement of CD4 and CD8 expressed on immature thymocytes induces activation of intracellular tyrosine phosphorylation pathways, J. Exp. Med. 170:1671 (1989).
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© 1992 Springer Science+Business Media New York
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Seong, R.H., Parnes, J.R. (1992). Alteration of T Cell Lineage Commitment by Expression of a Hybrid CD8/CD4 Transgene. In: Gupta, S., Waldmann, T.A. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation IV. Advances in Experimental Medicine and Biology, vol 323. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3396-2_11
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DOI: https://doi.org/10.1007/978-1-4615-3396-2_11
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