ANALYSIS OF T-CELL HYBRIDOMAS WITH AN UNUSUAL MHC CLASS II-DEPENDENT LIGAND SPECIFICITY

We have characterized two unusual T-cell hybridomas, 1E3 and 3B8, from H-2(k) mice immunized with I-A(b)-transfected L cells (H-2(k)), that are stimulated by L cells transfected with I-A(b), I-A(k) or I-E(b), b ut not by non-transfected L cells. These hybridomas could not be stimu lated by spleen cells from H-2(i3), H-2(k), H-2(b) or H-2(d) mice. Mon oclonal anti-I-A antibodies did not block their responses, suggesting that mouse major histocompatibility complex (MHC) class IT molecules m ay be peptide donors rather than restriction elements for them. The st imulation of these hybridomas by fibroblast targets was not blocked by an anti-H-2k(k).D-k-specific monoclonal antibody. Lipopolysaccharide (LPS)-activated splenic and peritoneal exudate cells from H-2(k), H-2( d), H-2(i3), H-2(b) as well as beta(2)-microglobulin-deficient. TAP-I- deficient and I-A alpha-deficient H-2(b) mice stimulated these hybrido mas, LPS could also activate a macrophage cell line, but not a B-cell liner to become stimulatory for 1E3. A rat antiserum against untransfe cted L cells specifically and significantly blocked the response of 1E 3. Thus. 1E3 may recognize a conserved murine MHC class II peptide loa ded in a TAP-1-independent fashion on a non-classical, monomorphic, be ta(2)-microglobulin-independent restriction element.