Genetic Control of the Immune Response

Abstract

In vitro antigen-induced tritiated thymidine uptake has been used to study the response of sensitized lymphocytes to (T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L in responder and nonresponder strains of mice. The reaction is T-cell and macrophage dependent. Highly purified T cells (91% Thy 1.2 positive) are also responsive, suggesting that this in vitro lymphocyte transformation system is not B-cell dependent. Lymphocytes from high and low responder mice stimulated in vitro react as responders and nonresponders in a pattern identical to that seen with in vivo immunization. Stimulation occurs only if soluble antigen is added at physiological temperatures; antigen exposure at 4°C followed by washing and incubation at 37°C fails to induce lymphocyte transformation. Stimulation is specific for the immunizing antigen and does not exhibit the serologic cross-reactivity which is characteristic of these three antigens and their respective antisera. The reaction can be inhibited by anti-H-2 sera but not by anti-immunoglobulin sera. The anti-immunoglobulin sera did, however, inhibit lipopolysaccharide or pokeweed mitogen stimulation. These results suggest that the Ir-1A gene(s) are expressed in T cells, and that there are fundamental physiologic differences between T- and B-cell antigen recognition.

I‐A Mutation resulted in a selective loss of an antigen‐specific Ir gene function

“…With this assay system, it was first established that the immune response to these antigens of restricted heterogeneity was controlled by an I-Ab region gene. As expected from previous studies [15,16] B10 mice were found to be responders to (TG)A-L and beef insulin, while B1O.A mice were nonresponders (see Table I). Since the recombinant strains BlO.A(4R) and BlO.MBR were both found to be non-responders, the proliferative responses to both (TG)A-L and beef insulin were shown to require a gene coded in the I-Ab subregion.…”

Mechanism of antigen binding by T cells: H‐2 (I‐A)‐restricted binding of antigen plus Ia by helper cells

“…Most of these experiments were performed at low temperatures, in the presence of sodium azide. The variable success of such experiments could be explained by the necessity of physiological temperature and metabolic energy for T cell antigen binding [31,321 and T cell stimulation [19,[33][34][35]. Similarly, difficulties in radioactive antigen suicide of helper cells were overcome by Basten et al, only when the cells were incubated at physiological temperature in the presence of adherent cells [36].…”

“…It has previously been shown that in contrast to B cells, T cells bind antigen optimally at physiological temperature, and that binding could be inhibited by sodium azide [19,201. This suggested that antigen binding to T cells in partially purified cul-C 3 H.SW nylon wool-purified T cells were pretreated with MF and subsequently labeled with 12'I-labeled (T,G)-A--L for different periods of time.…”

Control of B-lymphocyte function. I. Inactivation of mitogenesis by interactions with surface immunoglobulin and Fc-receptor molecules.

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The role of surface immunoglobulin (Ig) in triggering B-lymphocyte responses is not yet clear. For several years it has been known that anti-Ig antibodies can interfere with the activation of B cells by mitogens (1)(2)(3)(4)(5). Whether this block is external, interfering with the mitogenic receptor, or internal, affecting deeper features of the cells' metabolism, is not yet established.Anti-Ig antibodies have a particularly deleterious effect on the immature B lymphocyte (6), suggesting that surface Ig may control the state of differentiation and activation of the B cell.

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