Discrimination of human CD4 T cell clones based on their reactivity with antigen-presenting T cells.
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 gamma] did not change the proliferative response of the clones, which was consistent throughout an observation period of greater than 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.
Wyss-Coray
T
T
Institute for Clinical Immunology, Inselspital, Bern, Switzerland.
Brander
C
C
Frutig
K
K
Pichler
W J
WJ
D000938:Antigen-Presenting Cells / Q000502:physiology*; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D018106:CD28 Antigens; D015704:CD4 Antigens / Q000032:analysis; D018956:CD5 Antigens; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells; D016207:Cytokines / Q000494:pharmacology; D006682:HLA-DP Antigens / Q000032:analysis; D059868:HLA-DP beta-Chains; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D015704:CD4 Antigens; D018956:CD5 Antigens; D016207:Cytokines; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C056284:HLA-DPw4 antigen; D002118:Calcium