Heat-stable antigen is a costimulatory molecule for CD4 T cell growth.
Optimal induction of clonal expansion by normal CD4 T cells requires a ligand that can engage the T cell receptor as well as functionally defined costimulatory activity on the same antigen-presenting cell surface. While the presence of effective costimulation induces proliferation, T cell receptor ligation in its absence renders T cells inactive or anergic. The molecular basis of this costimulatory activity remains to be defined. Here we describe a monoclonal antibody that can block the costimulatory activity of splenic accessory cells. Treatment with this antibody not only blocks the proliferation of CD4 T cells to a T cell receptor ligand, but also induces T cell nonresponsiveness to subsequent stimulation. Sequence analysis of the antigen recognized by this antibody indicates that it recognizes a protein that is identical to heat-stable antigen. Gene transfer experiments directly demonstrate that this protein has costimulatory activity. Thus, heat-stable antigen meets the criteria for a costimulator of T cell clonal expansion.
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Y
Y
Liu
B
B
Jones
A
A
Aruffo
K M
KM
Sullivan
P S
PS
Linsley
C A
CA
Janeway
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D051927:CD24 Antigen; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D006017:Glycolipids / Q000378:metabolism; D017261:Glycosylphosphatidylinositols; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010716:Phosphatidylinositols / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology; D014162:Transfection; D010738:Type C Phospholipases / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D051927:CD24 Antigen; D017252:CD3 Complex; C497890:Cd24a protein, mouse; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D010738:Type C Phospholipases