Activation of T lymphocytes via monoclonal antibodies against rat cell surface antigens with particular reference to CD2 antigen.
In the rat, monoclonal antibodies (mAbs) against the T-lymphocyte receptor (TCR), CD3 antigen and CD2 antigen are mitogenic for T lymphocytes. Antibodies against CD43 (leukosialin) and CD5 are not, but can enhance the effects of other stimuli. Activation of a T-lymphocyte cell line in terms of triggering an increase in free cytoplasmic Ca2+ [( Ca2+]i) was mediated by mAbs against Class 1 MHC and CD4 in addition to the mitogenic mAbs. In the presence of non-activating levels of anti-TCR mAb a strong synergistic signal was seen with anti-CD4, but incubation with anti-CD4 prior to activation with anti-CD3 inhibited the CD3 signal. Stimulation of DNA synthesis in resting T cells via anti-CD2 mAbs required a combination of two non-competitive antibodies and addition of a third anti-CD2 mAb inhibited the activation. The anti-CD2 mAbs were active on all types of mature T cells from peripheral lymphoid organs and the thymus, but cells in the thymus that lacked a TCR could not be activated via CD2. Rat CD2 was transfected into Jurkat cells and cross-linking with anti-rat CD2 mAbs gave an increase in [Ca2+]i similar to that seen with an anti-human CD3 mAb. All three types of anti-rat CD2 mAbs gave a signal including the mAb that inhibited mitogenesis. Signal transduction via CD2 was not seen in L cells and was only weakly observed in TCR-ve Jurkat cells that had been transfected with rat CD2. The cytoplasmic domain of transfected CD2 was shown to be important for the signal transduction since no increase in [Ca2+]i could be triggered in cells expressing mutant CD2 that lacked the cytoplasmic domain. Mutant forms with increasing lengths of cytoplasmic domain showed functions that progressively approached that of the native function.
Beyers
A D
AD
MRC Cellular Immunology Research Unit, Sir William Dunn School of Pathology, University of Oxford, U.K.
Barclay
A N
AN
Law
D A
DA
He
Q
Q
Williams
A F
AF
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D018801:CD2 Antigens; D002118:Calcium / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D051381:Rats; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D011971:Receptors, Immunologic; D002118:Calcium