Heat-stable antigen is a costimulatory molecule for CD4 T cell growth

doi:10.1084/jem.175.2.437

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Heat-stable antigen is a costimulatory molecule for CD4 T cell growth

Y Liu, B Jones, A Aruffo, KM Sullivan, PS Linsley and CA Janeway Jr
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510.

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.
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