1. Affinity enhancement and transmembrane signaling are associated with distinct epitopes on the CD8 alpha beta heterodimer.
- Author
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Eichmann K, Ehrfeld A, Falk I, Goebel H, Kupsch J, Reimann A, Zgaga-Griesz A, Saizawa KM, Yachelini P, and Tomonari K
- Subjects
- Animals, Lymphocyte Activation, Lymphocyte Culture Test, Mixed, Mice, Mice, Inbred Strains, T-Lymphocytes, Cytotoxic immunology, Antigens, CD physiology, CD8 Antigens physiology, Epitopes analysis, Receptors, Antigen, T-Cell physiology, Signal Transduction
- Abstract
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.
- Published
- 1991