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 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(55)Lys(36)Phe(9))(n) (GLφ). In this paper we use the newly developed technology of T lymphocyte cloning to establish unequivocally the existence of such cells specific for GLφ and to generalize their existence by showing that F(1)- specific cells can be isolated from T cell populations primed to poly(Glu(60)Ala(30)Tyr(10))(n) (GAT) where such clones represent only a minor subpopulation of cells. Gl.4b-primed B10.A(5R) and GAT-primed (B10.A × 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 GLφ-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 GILφ but only in the presence of nonimmune, irradiated spleen cells bearing (B10.A × B10)F(1) or the syngeneic B 10.A(5R) recombinant MHC haplotype. Spleen cells from either the B10 or B 10.A parental strains failed to support a proliferative response, even when added together. (B10 × B10.D2)F(1) and (B10 × 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 GL[phi} in association with the β(AE)(b)-α(E) (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 β(AE)(b)-αE Ia molecule. Y-17 completely inhibited the proliferative response of a GLφ-specific clone but had no effect on the response of either a PPD-specific or GAT-specific clone, both of which required the β(A)-α(A) 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.

Serological Evidence for a Defect in RT1.B (I‐a) Expression by the Bdix Rat Strain

“…Early studies of class 11-associated immune response genes in mice revealed the phenomenon of Zr gene complementation, in which an F1 hybrid between two low or nonresponder mouse strains for a particular antigen was found to be a high responder (Stimpfling & Durham, 1972;Dorf et al, 1975). A number of the experimental cases of this were eventually found to be explained by the phenotypic 'rescue' of I-E chains from En mouse strains by association with complementing chains from the second parent of the F, (Sredni et al, 1981). It is interesting to recall, in the light of the present findings, that one of the cases of Zr gene complementation in the rat, described by Giinther and Rude (1975), involved RTld.…”

Genetic Control of the Immune Response to Haemoglobin

“…The recent availability of anti-Ia monoclonal antibodies (Hammerling et al, 1979;Ozato et al, 1980;Pierres ef al., 1980) has made possible more detailed serological analyses of Ir gene function (Harris et al, 1980;Hodes et al, 1980;Lerner et al, 1980;Napom et al, 198 1). Although data from inhibition experiments using anti-Ia monoclonal antibodies must be interpreted cautiously (Dubreuil et al, 1982), such experiments have permitted insights into the role of Ia determinants in responses to protein antigens Correspondence: Dr Chella S. David, Department of Immunology, Mayo Clinic and Medical School, Rochester, MN 55905, U.S.A. (Fathman el al., 1981;Srendi et al, 1981). We report here the confirmation of genetic mapping data by serological and functional assays.…”

Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation

“…It was very surprising that the B 10.A(5R) clone responded better to moth fragment 81-103 with the B10.A Ia molecule than with its own Ia molecule; that is, the B10.A(5R) clone appeared to be heteroclitic for the B10.A restriction element. This is not a general finding for all B10.A(5R) clones because PPD and Gl_4b-specific B10.A(5R) clones cannot be stimulated with antigen in the presence of B 10.A spleen cells (26). It is also not related to the responder status of the donor of the presenting cells because B10.S(gR) (ssskkddd) spleen cells would not present any of the cytochrome c fragments to the B 10.A(5R) clone (see Table I), even though the B 10.S(9R) is a high responder to both moth and pigeon cytochrome c. 3 Thus, the Ia heteroclicity appears to be a specific degeneracy associated with the receptor(s) on moth cytochrome c-reactive B10.A(5R) and B10.A clones.…”