In vitro evidence from anti-hapten antibody responses for T helper and suppressor cells directed against major histocompatibility antigens in the mouse. Participation of i region determinants in the induction of T helper cells

Vogt, P.; Simpson, E.

European Journal of Immunology 9(7): 561-569


ISSN/ISBN: 0014-2980
PMID: 91525
DOI: 10.1002/eji.1830090712
Accession: 068520491

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The antibody response to murine alloantigens is thought to be thymus-dependent. In this study, H-2 and H-minor antigens presented on the surface of cells were used as particulate carriers and 2,4,6-trinitrophenyl (TNP) was used as a hapten. To study conditions for the induction of T [thymus-derived] helper and T suppressor cells directed against such antigens, T cell donor mice of a given inbred strain were primed with spleen cells of another inbred strain differing in distinct subregions of its H-2 haplotype and/or differing in its H-minor haplotype. Spleen T cells of mice in vivo allogeneically (carrier)-primed in this way were cocultured in vitro with splenic in vivo TNP (hapten)-primed B [bone marrow-derived] cells plus irradiated TNP-conjugated spleen cells (hapten-carrier conugate) from the haplotype used for carrier priming. The anti-hapten antibody response was taken as a quantitative indicator of helper activity. Suppression was tested by measuring the reduction of the antibody-forming cell response of in vivo TNP or sheep red blood cell (SRBC)-primed B cells restimulated in vitro with homologous antigen in the presence of allogeneically primed T cells. Helper cell functions were clearly demonstrated when donors of T cells were primed to Ia antigens. Additional priming to K and/or D antigens yielded help and suppression simultaneously, priming to K and/or D antigens alone and in some cases to H-minor antigens antigens yielded no help but resulted in strong suppression. The effect of the helper cells was carrier-specific occurring only in the presence of the relevant carrier, whereas the suppressor T cells were of the nonspecific type suppressing both anti-TNP and anti-SRBC responses in the absence of any restimulating carrier. The helper effect was seen not only when the hapten was conjugated to the appropriate (allogeneic) cells but also when it was presented on an unrelated carrier (syngeneic cells) provided that the specific nonhaptenated carrier was present. Possible recognition mechanisms were discussed.