Expression of different CD8 isoforms on distinct human lymphocyte subpopulations

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Abstract
Human CD8+ lymphocyte subpopulations were analyzed for their expression of CD8 α and CD8 β 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 γ/δ, and CD4+CD8+ T cell clones express exclusively CD8 α gene products. Structural analysis of CD8 molecules demonstrates that CD8 α+/β− T lymphocytes surface express 75-kDa CD8 α/α homodimers whereas CD8 α/β 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 α/α homodimers and α/β heterodimers on CD8 α/β+ cells. Importantly, we found that the two CD8 isoforms behave functionally different. Thus, in contrast to CD8 α/β+/CD8 α/α+ T lymphocytes, cytolytic activity of CD8α/β−/CD8 α/α+ T cell clones was not inhibited by anti-CD8 monoclonal antibodies and the latter were not induced to proliferate following CD3/CD8 cross-linking.