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Expression of different CD8 isoforms on distinct human lymphocyte subpopulations
U Moebius1, G Kober, A L Griscelli
1Abteilung Angewandte Immunologie, Deutsches Krebsforschungszentrum, Heidelberg, FRG.
Insights
Human CD8+ lymphocytes express CD8 alpha and beta subunits, forming distinct homodimers and heterodimers. These CD8 isoforms exhibit differential functional activity, impacting T cell responses and cytolytic activity.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD8+ lymphocytes play a crucial role in adaptive immunity.
- Understanding the composition and function of CD8 variants is essential for immune research.
Purpose of the Study:
- To analyze the expression of CD8 alpha and beta subunits in human CD8+ lymphocyte subpopulations.
- To investigate the structural and functional differences between CD8 isoforms.
Main Methods:
- Analysis of peripheral blood lymphocytes and cloned T cell subpopulations.
- Structural analysis of CD8 molecules using techniques like peptide mapping.
- Functional assays to assess cytolytic activity and proliferation.
Main Results:
- CD3- natural killer cells, T cell receptor gamma/delta, and CD4+CD8+ T cell clones exclusively express CD8 alpha gene products.
- CD8 alpha+/beta- T lymphocytes express CD8 alpha/alpha homodimers (75 kDa).
- CD8 alpha/beta lymphocytes express both CD8 alpha/alpha homodimers (75 kDa) and CD8 alpha/beta heterodimers (67 kDa).
- CD8 alpha/alpha homodimers and CD8 alpha/beta heterodimers exhibit distinct functional properties, affecting T cell cytolytic activity and proliferation responses.
Conclusions:
- Human CD8+ lymphocytes express diverse CD8 isoforms with differential functional capacities.
- The distinct behaviors of CD8 alpha/alpha homodimers and CD8 alpha/beta heterodimers have significant implications for T cell-mediated immunity.
Abstract:
Human CD8+ lymphocyte subpopulations were analyzed for their expression of CD8 alpha and CD8 beta subunits. Investigations with uncloned peripheral blood lymphocytes as well as cloned human natural killer and T cell subpopulations demonstrate that CD3- natural killer cells, T cell receptor gamma/delta, and CD4+CD8+ T cell clones express exclusively CD8 alpha gene products. Structural analysis of CD8 molecules demonstrates that CD8 alpha+/beta- T lymphocytes surface express 75-kDa CD8 alpha/alpha homodimers whereas CD8 alpha/beta lymphocytes express concomittantly two CD8 isoforms of different molecular masses (67 kDa and 75 kDa, respectively). Peptide mapping of these latter two isoforms suggests that CD8 is expressed as alpha/alpha homodimers and alpha/beta heterodimers on CD8 alpha/beta+ cells. Importantly, we found that the two CD8 isoforms behave functionally different. Thus, in contrast to CD8 alpha/beta+/CD8 alpha/alpha+ T lymphocytes, cytolytic activity of CD8 alpha/beta-/CD8 alpha/alpha+ T cell clones was not inhibited by anti-CD8 monoclonal antibodies and the latter were not induced to proliferate following CD3/CD8 cross-linking.