The CD8β ectodomain contributes to the augmented coreceptor function of CD8αβ heterodimers relative to CD8αα homodimers

Within the lymphoid compartment, CD8 is expressed either as an alpha alpha homodimer or as an alpha beta heterodimer. Prior functional characterization of CD8 alpha transfectants has demonstrated that CD8 alpha alpha homodimers can reconstitute T cell responses in the absence of the CD8 beta subunit. In order to now examine the role of CD8 beta in TCR recognition, the CD8 alpha cDNA alone or in combination with CD8 beta cDNA was transfected into the mouse T cell hybridoma, N15wt, specific for VSV8/K-b. Comparison of antigen-induced IL-2 production reveals that CD8 alpha beta(+) transfectants are 100-fold more sensitive in molar terms of peptide than CD8 alpha alpha(+) transfectants. This enhancement of IL-2 production is independent of CD8 alpha or CD8 beta cytoplasmic tails as demonstrated by analysis of cytoplasmic deletion mutants CD8 alpha'beta, CD8 alpha beta', and CD8 alpha'beta'. These results indicate that the ectodomain of the CD8 beta chain greatly enhances the coreceptor function of the CD8 alpha beta molecule, at least for certain class I MHC restricted cup TCRs. (C) 1999 Academic Press.