Possible T4‐HLA class II interaction as an essential event in antigen‐specific helper T lymphocytedependent B cell activation

Abstract

We have previously shown that the interaction between influenza virus-specific helper T lymphocytes and B lymphocytes is HLA class II restricted (Fischer, A. et al., Eur. J. Immunol. 1985. 15: 620). In the present study, we used a panel of antibodies specific for the T4 and HLA-DR molecules to investigate the role of both structures in T-B lymphocyte interaction. Several anti-T4 monoclonal antibodies were shown to block the in vitro antibody production to A/Bangkok influenza virus while they were unable to inhibit the A/Bangkok-induced proliferation of specific helper T cell clones. Some anti-HLA-DR monoclonal antibodies inhibited the antibody production to A/Bangkok, the target of the inhibition being either monocytes or B lymphocytes. The incubation of helper T cell clones with an infra-inhibitory concentration of anti-T4 antibody and of B lymphocytes with an infra-inhibitory concentration of anti-HLA-DR antibody resulted in a mutual enhancement of inhibition. Such synergistic interactions were not observed using combinations of anti-T4 and anti-B membrane structures such as p35 or LFA-1 or anti-HLA-DR and anti-T membrane structures such as T11 or LFA-1. First, these results indicate that the T4 molecule plays an essential role in T-B cell interaction even when it is not absolutely required for T cell proliferation. Second, they strongly suggest that the T4 molecule directly interacts with HLA-DR at the B cell surface. Whether such interaction is required to enhance the stability of T3/T cell receptor-antigen plus HLA class II association or whether T4-HLA-DR may transduce a signal towards B lymphocytes that is required in B cell activation remains unknown.

Activated human T cells express a ligand for the human B cell‐associated antigen CD40 which participates in T cell‐dependent activation of B lymphocytes

“…In addition adhesion molecules like ICAM-1 and LFA-1 shared with other cell types can mediate binding [24]. Class I1 molecules on human Bcells have been shown to signal in a similar manner to surface immunoglobulin [25], and furthermore engagement between adhesion molecules also seems to be important [26,27,281. It is tempting to speculate that cognate engagement between peptide-presenting B cells and antigen-specific T cells leads to a primary signal which does not involve CD40 or its ligand, but that subsequent up-regulation of the CD40 ligand plays a role in the B cell-induced proliferation.…”

Intracellular events associated with inhibition of B cell activation by monoclonal antibodies to HLA class II antigens

“…The responsiveness could be partially blocked by the addition of anti-Ia antibodies, indicating that T cells deliver an important signal to B cells by interacting with surface MHC class I1 molecules. Data favoring a CDCHLA class I1 interaction as an important event in antigen-specific Th lymphocyte-dependent B cell activation, has also been presented [39]. Based on the tendency for anti-MHC class I1 mAb to induce rather strong cell aggregates (data not shown), one may speculate that also B-B cell interactions are important in the inhibition of B cell proliferation by these mAb.…”

Modulation of CD4 Antigen Expression on the Lymphocyte Surface by Immunosuppressive Acidic Protein in Cancer Patients

“…It is well understood that the CD4 antigen defines a subset of mature T lymphocytes which possesses both reg ulatory and antigen recognition functions and plays a cen tral role in the circuit of immune response [9], including antigen-specific CD4+ helper T lymphocyte-dependent B cell activation [10] and the cytotoxic reaction mediated by the CD4+ cytotoxic T cells [11]. Such functions of the CD4+ subset are restricted by class II MHC antigen [9], in which the CD4 antigen binds directly with class II MHC antigen [12,13].…”