Mechanisms involved in the Ir-gene control of T suppressor cell response to lactate dehydrogenase B.
It has now been widely accepted that the immune response (Ir)-gene control of T helper (Th)-cell responses reflects the influence of class II major histo-compatibility complex (MHc) molecules on T-cell specificity. This influence can either be exerted during T-cell ontogeny and result in class II allele-dependent differences in the T-cell repertoire, or manifests itself during the immune response as a restricted capacity of class II molecules to associate with foreign antigens in a form recognizable by Th cells. Depending on the level at which class II Mhc molecules act, the cause of nonresponsiveness to certain antigens can be either the absence of the relevant clones from the T-cell repertoire (as a result of Mhc-dependent positive or negative selection mechanisms), or the incapability of a particular class II molecule to form a complex with a foreign antigen on the surface of antigen presenting cells (APC). It is well known that T suppressor (Ts)-cell responses can also be under Ir-gene control, as reflected in the Mhc-dependence of Ts cell-generation in response to certain antigens. However, the mechanisms involved in this Ir-gene control are less well understood. We have used here the immune response to lactate dehydrogenase B (LDHB) as a model to explore the mechanisms causing absence of suppression ("Ts-cell nonresponsiveness"). The LDHB system is suitable to investigate this question, because the LDHB-specific Ts cells are Mhc-restricted, and only two allelic forms, b and k, of the E beta class II polypeptide can serve as restriction elements for Ts-cell generation; mouse strains not expressing these molecules are Ts-cell nonresponders. We applied here the methods previously used to analyse nonresponsiveness of Th cells to the Ts-cell response. The approach was to generate LDHB-specific Ts cells in vitro, by presenting the antigen on Mhc-disparate APC (allorestricted Ts cells). The results have demonstrated that Ts cells from two representative Ts-responder strains can be generated in the context of several but not all allogeneic E molecules. The non-responsiveness observed in certain allogeneic T cell-APC combinations could not be explained by defective antigen presentation. Thus, these cases of Ts-cell nonresponsiveness, similar to Th-cell nonresponsiveness, might have resulted from the absence of the relevant T-cell clones from the repertoire of the strain tested.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000950:Antigens, Ly; D005802:Genes, MHC Class II; D006183:H-2 Antigens; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000276:immunology; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000950:Antigens, Ly; D006183:H-2 Antigens; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase