The dependence for leukocyte function-associated antigen-1/ICAM-1 interactions in T cell activation cannot be overcome by expression of high density TCR ligand

The leukocyte-specific integrin, LFA-1, can enhance T cell activation. Howe ver, it is unclear whether the binding of LFA-1 to its ligand, ICAM-1, func tions through intercellular adhesion alone, resulting in an augmentation of the TCR signal, or involves an additional LFA-l-mediated cellular signal t ransduction pathway. We have previously shown that naive CD4+ lymph node T cells, isolated from DO11.10 TCR transgenic mice, are activated by increasi ng doses of exogenous OVA peptide presented by transfectants expressing bot h class II and ICAM-1, but not by cells expressing class II alone. To deter mine whether LFA-1/ICAM-1 interactions were simply enhancing the presentati on of low concentrations of specific MHC/peptide complexes generated from e xogenously added peptide, we transfected cells with class II that is covale ntly coupled to peptide, alone or in combination with ICAM-1. These cells e xpress 100-fold more specific class II/peptide complexes than can be loaded onto class II-positive cells at maximum concentrations of exogenous peptid e. Despite this high density of TCR ligand, activation of naive CD4+ T cell s still requires the coexpression of ICAM-1, LFA-1/ICAM-1 interactions are not required for effective conjugate formation and TCR engagement because p resentation of class II/peptide complexes in the absence of ICAM-1 does ind uce up-regulation of CD25 and CD69, Thus, high numbers of engaged TCR canno t compensate for the lack of LFA-1/ICAM-1 interactions in the activation of naive CD4+ T cells.