MHC CLASS-II T-CELL RECEPTOR INTERACTIONS POTENTIATE SECRETION OF IGGBUT NOT IGM IN RESPONSE TO T-DEPENDENT ANTIGENS

We have examined whether the interaction of peptide-loaded MHC molecul es on the surface of B-cells with antigen-specific T-cell receptors (T CRs) enhances Ig secretion in the presence of other antigen-independen t interactions in vitro. B-cells specific for region 25-40 of beta-lac toglobulin (beta-LG) were stimulated in a T-cell dependent manner usin g plasma membranes (PM) derived from two different T-helper (Th) clone s, culture supernatants of activated Th2 cells and beta-LG as a specif ic antigen. PM were obtained from either the beta-LG-specific T-cell c lone H1.1 which can mediate specific TCR/MHC class II interactions as well as antigen-independent ones or from the D10 clone which bears a T CR of an irrelevant specificity and thus, can only mediate antigen-ind ependent interactions. IgG, but not IgM, secretion was specifically en hanced by H1.1 PM, but not D10 PM in the presence of beta-LG. Furtherm ore, a blockade of TCR/MHC class II interactions using either anti-T-c ell receptor, beta or anti-CD4 monoclonal antibodies inhibited this en hanced IgG secretion in response to beta-LG. The results show that whi le antigen-independent interactions between T-and B-cells can enhance secretion of IgM antibodies, specific interactions between TCRs and pe ptide:MHC complexes stimulate B-cells to enhance secretion of IgG but not IgM antibodies. This mechanism may contribute to antibody secretio n only from B-cells activated through cognate interaction in vivo. (C) 1998 Elsevier Science B.V. All rights reserved.