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The Journal of Immunology, Vol 147, Issue 7 2075-2081, Copyright © 1991 by American Association of Immunologists


ARTICLES

Affinity enhancement and transmembrane signaling are associated with distinct epitopes on the CD8 alpha beta heterodimer

K Eichmann, A Ehrfeld, I Falk, H Goebel, J Kupsch, A Reimann, A Zgaga-Griesz, KM Saizawa, P Yachelini and K Tomonari
Max-Planck-Institut fur Immunbiologie, Freiburg, Germany.

CD8 is a heterodimeric membrane glycoprotein on MHC class I-restricted T lymphocytes that cooperates with the alpha beta CD3 TCR in the recognition of MHC class I molecules presenting antigenic peptides. Co- operation has two components: enhancement of the affinity of MHC/peptide-TCR interaction, and signal transduction through the T cell membrane. The cytolytic function of CTL is primarily dependent on the affinity-enhancement component of CD8-TCR cooperation whereas activation of resting CD8+ T cells is primarily dependent on transmembrane signaling. Using a panel of mAb, two to the alpha-chain and three to the beta-chain of CD8, we investigated the relationships between epitopes and functional regions of the CD8 molecule. Two of the antibodies, one to the alpha-chain and one to the beta-chain of CD8, inhibit the cytolytic function of CTL but not the generation of CTL from resting T cells. Another two antibodies, also one to the alpha- and one to the beta-chain, inhibited the generation of CTL while enhancing the cytolytic function of CTL. These results suggest that both the alpha- and beta-chain of CD8 possess two distinct regions, one involved in affinity enhancement and the other in transmembrane signaling. The former may be the MHC class I-binding region whereas the latter may associate with the alpha beta CD3 TCR. The data can explain the apparent functional equivalence of CD8 alpha alpha homodimers and alpha beta heterodimers.


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M. A. Daniels and S. C. Jameson
Critical Role for CD8 in T Cell Receptor Binding and Activation by Peptide/Major Histocompatibility Complex Multimers
J. Exp. Med., January 17, 2000; 191(2): 335 - 346.
[Abstract] [Full Text] [PDF]




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