Expression of CD4 can confer major histocompatibility complex class II-associated superantigen reactivity upon a T cell receptor derived from a CD8-dependent cytotoxic T lymphocyte clone.

It has been shown that reactivity against major histocompatibility complex (MHC) class II-associated Mlsa determinants is mainly mediated by CD4+ V beta 6+ T cells. 3F9 is a CD8+ CTL clone which is specific for the alloantigen H-2Db. While 3F9 is V beta 6+, it is not Mlsa reactive, presumably because it does not express CD4. 3F9 utilizes the same T cell receptor (TcR) V alpha V beta combination as LB2, a CD4+ T helper clone specific for chicken red blood cells (cRBC)/I-Ab and yet differs from LB2 in the junctional sequences in both TcR chains. CD4+ CD8- and CD4-CD8- hybridomas expressing the 3F9 TcR were tested for reactivity against Mlsa and cRBC/I-Ab. Only the CD4+CD8- hybridomas were Mlsa reactive, and antibody inhibition studies revealed that this reactivity was both CD4 and MHC class II dependent. Therefore the expression of the CD4 molecule can make an MHC class I-restricted TcR Mlsa reactive. Neither type of hybridoma reacted against cRBC, thus the main difference in the antigen reactivity between 3F9 and LB2 lies in the TcR junctional regions.