T lymphocyte enriched murine peritoneal exudate cells. III. Inhibition of antigen induced T lymphocyte proliferation with anti Ia antisera

R. H. Schwartz, C. S. David, D. H. Sachs, W. E. Paul

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102 Scopus citations

Abstract

The recent development of a reliable murine T lymphocyte proliferation assay has facilitated the study of T lymphocyte function in vitro. In this paper, the effect of anti histocompatibility antisera on the proliferative response was investigated. The continuous presence of anti Ia antisera in the cultures was found to inhibit the responses to the antigens poly (Glu58Lys38Tyr4) [GLT], poly (Tyr, Glu) poly D,L Ala poly Lys [(T,G) A L], poly (Phe, Glu) poly D,L Ala poly Lys [(phi,G) A L], lactate dehydrogenase H4, staphylococcal nuclease, and the IgA myeloma protein, TEPC 15. The T lymphocyte proliferative responses to all of these antigens have previously been shown to be under the genetic control of major histocompatibility linked immune response genes. The anti Ia antisera were also capable of inhibiting proliferative responses to antigens such as PPD, to which all strains respond. In contrast, antisera directed solely against H 2K or H 2D antigens did not give significant inhibition. Anti Ia antisera capable of reacting with antigens coded for by genetically defined subregions of the I locus were capable of completely inhibiting the proliferative response. In the two cases studied, GLT and (T,G) A L, an Ir gene controlling the T lymphocyte proliferative response to the antigen had been previously mapped to the same subregion as that which coded for the Ia antigens recognized by the blocking antisera. Finally, in F1 hybrids between responder and nonresponder strains, the anti Ia antisera showed haplotype specific inhibition. That is, anti Ia antisera directed against the responder haplotype could completely block the antigen response controlled by Ir genes of that haplotype; anti Ia antisera directed against Ia antigens of the nonresponder haplotype gave only partial or no inhibition. Since this selective inhibition was reciprocal depending on which antigen was used, it suggested that the mechanism of anti Ia antisera inhibition was not cell killing or a nonspecific turning off of the cell but rather a blockade of antigen stimulation at the cell surface. Furthermore, the selective inhibition demonstrates a phenotypic linkage between Ir gene products and Ia antigens at the cell surface. These results, coupled with the known genetic linkage of Ir genes and the genes coding for Ia antigens, suggest that Ia antigens are determinants on Ir gene products.

Original languageEnglish (US)
Pages (from-to)531-540
Number of pages10
JournalJournal of Immunology
Volume117
Issue number2
StatePublished - Dec 1 1976

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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