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

B. Sredni, L. A. Matis, E. A. Lerner, W. E. Paul, R. H. Schwartz

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The existence of T cells specific for soluble antigens in association with unique F 1 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 (Glu 55Lys 36Phe 9)(n) (Glo). In this paper we use the newly developed technology of T lymphocyte cloning to establish unequivocally the existence of such cells specific for GLo and to generalize their existence by showing that F 1-specific cells can be isolated from T cell populations primed to poly(Glu 60Ala 30Tyr 10)(n) (GAT) where such clones represent only a minor subpopulation of cells. GL0-primed B10.A(5R) and GAT-primed (B10.A x B10)F 1 lymph node T cells were cloned in soft agar, and the colonies that developed were picked and expanded in liquid culture. The GLo-specific T cells were then recloned under conditions of high-plating efficiency to ensure that the final colonies originated from single cells. T cells from such rigorously cloned populations responded to stimulation with GLo but only in the presence of nonimmune, irradiated spleen cells bearing (B10.A x B10)F 1 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 x B10.D2)F 1 and (B10 x B10.RIII)F 1 spleen cells also supported a proliferative response but (B10 B10.Q)F 1 and (B10 x B10.S)F 1 spleen cells did not. These results suggested that the T cell clones were specific for GLo in association with the βAE(b)-αE(k,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 determinant on the βAE-αE Ia molecule. Y-17 completely inhibited the proliferative response of a GLo-specific clone but had no effect on the response of either a PPD-specific or GAT-specific clone, both of which required the βA-αA Ia molecule as their restriction element. No evidence could be found for the involvement of suppressor T cells in this inhibition. We therefore conclude that the phenomenon of F 1-restricted recognition by proliferating T cells results from the presence of antigen-specific clones that must recognize unique F 1 or recombinant Ia molecules on the surface of antigen-presenting cells in addition to antigen in order to be stimulated.

Original languageEnglish
Pages (from-to)677-693
Number of pages17
JournalJournal of Experimental Medicine
Issue number3
StatePublished - 1 Mar 1981
Externally publishedYes


FundersFunder number
National Institute of Allergy and Infectious DiseasesR01AI014579


    Dive into the research topics of 'Antigen-specific T cell clones restricted to unique F 1 major histocompatibility complex determinants. Inhibition of proliferation with a monoclonal anti-ia antibody'. Together they form a unique fingerprint.

    Cite this