Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex.

TLDR

The authors generated monoclonal antibodies against the HLA‑A3–specific CT8III cytotoxic T‑cell clone to identify clonotypic surface molecules that mediate its antigen‑recognition function. They used antibody‑induced modulation and competitive binding assays to compare the clonotypic structures with known T‑cell surface molecules, including the T3 complex. The anti‑Ti1A and anti‑Ti1B antibodies bound only CT8III, inhibited its cytotoxicity and proliferation while sparing other clones, enhanced IL‑2 responsiveness, and immunoprecipitated two distinct 49 kDa and 43 kDa proteins that are associated with but distinct from the ubiquitous T3 molecule.

Abstract

Monoclonal antibodies were produced against a human cytotoxic T cell clone, CT8III (specificity: HLA-A3), with the view of defining clonally restricted (clonotypic) surface molecules involved in its antigen recognition function. Two individual antibodies, termed anti-Ti1A and anti-Ti1B, reacted exclusively with the CT8III clone when tested on a panel of 80 additional clones from the same donor, resting or activated T cells, B cells, macrophages, thymocytes, or other hematopoietic cells. More importantly, the two antibodies inhibited cell-mediated killing and antigen-specific proliferation of the CT8III clone but did not affect the functions of any other clone tested. This inhibition was not secondary to generalized abrogation of the CT8III clone's function, because interleukin 2 responsiveness was enhanced. To examine the relationship of the structures defined by anti-clonotypic antibodies with known T cell surface molecules, antibody-induced modulation studies and competitive binding assays were performed. The results indicated that the clonotypic structures were associated with, but distinct from, the 20,000-mol wt T3 molecule expressed on all mature T lymphocytes. Moreover, in contrast to anti-T3, anti-Ti1A and anti-Ti1B each immunoprecipitated two molecules of 49,000 and 43,000-mol wt from 131I-labeled CT8III cells under reducing conditions. The development of monoclonal antibodies to such polymorphic T cell surface structures should provide important probes to further define the surface receptor for antigen.