Accessory molecules and T cell activation I. Antigen receptor avidity differentially influences T cell sensitivity to inhibition by monoclonal antibodies to LFA‐1 and L3T4

Abstract

A series of BALB/c-derived T hybridoma cells, capable of producing interleukin 2 (IL 2) in response to poly(Glu60, Ala30, Tyr10) (GAT) presented by syngeneic B lymphoma cells in the context of Ad restriction determinants, was used as a model system to evaluate the roles of LFA-1 and L3T4 accessory molecules in antigen-specific T cell activation. Examination of the antigen requirement for optimal IL 2 responses revealed marked differences in the apparent avidity of these cells for GAT/Ad complexes. A relationship was observed between this parameter and the susceptibility of T hybridoma cells to inhibition by monoclonal antibodies directed at 5 distinct epitopes of LFA-1, and at A beta d allodeterminants. In contrast, L3T4a-specific monoclonal antibodies were found to block in a similar fashion the antigen-specific IL 2 responses of T hybridoma cells, regardless of the apparent avidity of their antigen receptors. It was also shown that both L3T4+ and L3T4- T hybridoma cells were capable of recognizing GAT plus Ad with high avidity. Thus, the quality of T cell antigen recognition appears to critically influence the involvement of LFA-1, and only to a marginal extent that of L3T4, in antigen-specific T cell activation. The implications of these findings are discussed in the context of recent data indicating that L3T4 may not only be an Ia-binding protein.

Molecules and Regulation in Lymphocyte Migration

“…The latter finding points to an accessory role for LFA-1 similar to its envisaged functioning as an adhesion strengthening system in T-cell cytolysis or T-cell activation. It has been shown for antigeninduced T-cell proliferation that activation of T cells was more dependent on LFA-I the less the avidity conferred by the T-cell antigen receptor (Gougeon et al 1985, Regnier-Vigouroux et al 1986). We obtained analogous results with respect to lymphocyte-HEV interaction using sublines of lymphoma or T-cell hybridoma cells selected for different expression of the MEL-14-defined homing receptor (Fig.…”

Signal transduction through cd4 receptors: stimulatory vs. inhibitory activity is regulated by cd4 proximity to the cd31t cell receptor

“…Although considerable indirect evidence supports this hypothesis, the physiological role of CD4 during T cell activation is uncertain and remains the subject of controversy. Analysis of spontaneous CD4 loss variants [4], as well as gene transfer experiments [4, 51, suggests that the expression of [I 66121 CD4 augments T cell responses to specific antigen and that CD4 is particularly important when concentrations of antigen are suboptimal or when the avidity of the T cell for antigen plus MHC is low [6,71. Consistent with these observations, monoclonal antibodies (mAb) to CD4, when immobilized to the same solid support as mAb to the CD3/antigen receptor complex (CD3/Ti), augment CD3/Ti-induced T cell responses .…”

The role of lymphocyte function‐associated antigen 1 (LFA‐1) in the adherence of T lymphocytes to B lymphocytes

“…In vivo selection of functionally LFA-1-independent antigen-specific T cells may well have occurred. In patients with LAD, such LFA-1-independent T cells have been described, presumably with a high affinity for antigen [25,26]. It is worth noting that most of patients with LAD have normal in vitro and in vivo antigen-specific T cell responses [7].…”