Discrimination of human CD4 T cell clones based on their reactivity with antigen‐presenting T cells

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Abstract
In this report, we describe the discrimination of human T cell clones based on their reactivity with activated T cells as antigen‐presenting cells (APC). CD4+ T cell clones specific for peptide P30 of tetanus toxin (amino acids 947–967) and restricted to the DP4 molecule were established and tested for proliferation to peptide presented either by peripheral blood mononuclear cells (PBMC), Epstein‐Barr virus (EBV)‐transformed B cells or major histocompatibility complex (MHC) class II‐expressing T cells. We found two sets of T cell clones: one set proliferated to peptide presentation by PBMC, EBV‐transformed B cell lines (EBV‐B cells) and MHC class II+ T cells (termed T‐responder clones), while the other set of clones was only stimulated to proliferate, if the peptide was presented by PBMC or EBV‐B cells, but not by T cells (T‐nonresponder clones). Nevertheless, these T‐nonresponder clones recognized P30 also on T cells, as revealed by Ca2+ influx. The discrimination of the clones was not due to different avidities of the T cell receptors (TcR) of individual clones for the MHC‐peptide complex as T‐responder and T‐nonresponder clones had similar dose‐response curves to P30 presented by fixed EBV‐B cell lines. Addition of cytokines [interleukin (IL)‐1, IL‐2, IL‐4 and interferon γ] did not change the proliferative response of the clones, which was consistent throughout an observation period of >4 months. T‐nonresponder clones, exposed to P30 on MHC class II‐expressing T cells, became not anergic, as they could be restimulated by P30 presented on EBV‐B cells. The measurement of a panel of T cell activation markers and adhesion molecules on T‐responder and T‐nonresponder clones revealed a higher expression of the CD28 molecule on the T‐nonresponder clones. The data suggest that freshly cloned T cells can be differentiated by peptide presentation on classical (PBMC, EBV‐B cells) or non‐classical APC (class II+ T cells), and that this discrimination is further underlined by different levels of adhesion molecules.