Antigen-specific T cell clones restricted to unique F(1) major histocompatibility complex determinants. Inhibition of proliferation with a monoclonal anti-Ia antibody

Abstract

The existence of [murine] T cells specific for soluble antigens in association with unique F1 or recombinant major histocompatibility complex (MHC) gene products was first postulated from studies on the proliferative response of whole T cell populations to the antigen poly(Glu55Lys36Phe9)n (GL.phi.). The newly developed T lymphocyte cloning technology was used to establish unequivocally the existence of such cells specific for GL.phi. and to generalize their existence by showing that F1-specific cells can be isolated from T cell populations primed to poly(Glu60Ala30Tyr10)n (GAT) where such clones represent only a minor cell subpopulation. GL.phi.-primed B10.A(5R) and GAT-primed (B10.A .times. B10)F1 lymph node T cells were cloned in soft agar and the colonies that developed were picked and expanded in liquid culture. The GL.phi.-specific T cells were then recloned under high-plating efficiency conditions to ensure that the final colonies originated from single cells. T cells from such rigorously cloned populations responded to stimulation with GL.phi. but only in the presence of nonimmune, irradiated spleen cells bearing (B10.A .times. B10)F1 or the syngeneic B10.A(5R) recombinant MHC haplotype. Spleen cells from either the B10 or B10.A parental strains failed to support a proliferative response, even when added together. (B10 .times. B10.D2)F1 and (B10 .times. B10.RIII)F1 spleen cells also supported a proliferative response but (B10 .times. B10.Q)F1 and (B10.S)F1 spleen cells did not. These results suggested that the T cell clones were specific for GL.phi. in association with the .beta.AEb-.alpha.Ek,d,r. Ia molecule and that recognition required both gene products to be expressed in the same antigen-presenting cells. Support for this interpretation was obtained from inhibition experiments using the monoclonal antibody Y-17 specific for a .beta.AE-.alpha.E Ia molecule determinant. Y-17 completely inhibited the proliferative response of a GL.phi.-specific clone but had no effect on the response of either a purified protein derivative specific or GAT-specific clone, both of which required the .beta.A-.alpha.A Ia molecule as their restriction element. No evidence was found for suppressor T cell involvement in this inhibition. Evidently, the phenomenon of F1-restricted recognition by proliferating T cells results from the presence of antigen-specific clones that must recognize unique F1 or recombination Ia molecules on the antigen-presenting cell surface in addition to antigen in order to be stimulated.