T-cell receptor alpha chain plays a critical role in antigen-specific suppressor cell function.
Antigen-specific suppressor T-cell hybridomas release soluble suppressor factors (TsF) in the supernatant that modulate both in vivo delayed-type hypersensitivity and in vitro plaque-forming cell responses in an antigen-specific manner. To study the relationship between the T-cell receptor (TcR) and TsF, we developed a series of TcR alpha- or TcR beta- expression variants from suppressor T-cell hybridomas that expressed the CD3-TcR alpha/beta complex. We demonstrate that loss of TcR alpha but not TcR beta mRNA was accompanied by the concomitant loss of suppressor bioactivity. Homologous transfection of TcR alpha cDNA into a TcR alpha- beta+ clone reconstituted both CD3-TcR expression and suppressor function. Furthermore, suppressor activity from TcR beta- variants was specifically absorbed by antigen and anti-TcR alpha antibodies, but not by anti-CD3 or anti-TcR beta affinity columns. These data directly establish a role for the TcR alpha chain in suppressor T-cell function and suggest that the TcR alpha chain is part of the antigen-specific TsF molecule.
Kuchroo
V K
VK
Department of Pathology, Harvard Medical School, Boston MA 02115.
Byrne
M C
MC
Atsumi
Y
Y
Greenfield
E
E
Connolly
J B
JB
Whitters
M J
MJ
O'Hara
R M
RM
Collins
M
M
Dorf
M E
ME
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D001483:Base Sequence; D015152:Blotting, Northern; D017252:CD3 Complex; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D006825:Hybridomas; D006968:Hypersensitivity, Delayed / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D013491:Suppressor Factors, Immunologic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014162:Transfection
D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D009841:Oligonucleotides; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013491:Suppressor Factors, Immunologic; D004247:DNA