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T-cell inhibition of humoral responsiveness. II. Theory on the role of restrictive recognition in immune regulation.

A general theory is presented which deals with the finding that effector T-cell inhibitory and cytotoxic activity are K/D-restricted whereas effector T-cell cooperating activity and delayed-hypersensitivity are I-restricted. It is argued that this fact alone requires the T-cell receptor to be dual-recognative. Within the framework of the associative recognition (“two-signal”) theory, a dual-recognition model of restrictive recognition is proposed. The questions dealt with derive from our previous study (1): (1) Under what conditions may effector T-cell function be unrestricted? (2) Are paralysis and induction of antigen-sensitive t-cells restricted? (3) What determines restrictive specificity and the relationship between restriction and T-cell function? (4) What are the expected characteristics of the germ-line genes which encode the T-cell receptor?The elements of the minimal model are: (1) The T-cell expresses a receptor consisting of an anti-self MHC (S) site and an anti-antigen (X) site physically linked to each other and to a signal donor site. (2) The target cell has on its surface the antigenic determinant, X, and the restricting element, S(K/D or I), linked to a signal acceptor site. (3) Restricted signaling requires (a) an interaction between X and anti-X and (b) the positioning of the acceptor with respect to the donor, i.e. formation of a “synapse,” by an interaction between S and anti-S. (4) The acceptor linked to K/D can read inhibitory and cytotoxic signals whereas the acceptor linked to I can read cooperative and delayed-hypersensitivity signals. (5) The paralysis and induction of antigen-sensitive t-cells can be unrestricted (the anti-S site of the t-cell need not be occupied). All signals to the t-cell are initiated uniquely by the X-anti-X interaction. (6) Positive selection in the thymus via an S anti-S interaction between a pre-t-cell expressing anti-S with a “restricting cell,” expressing S, fixes the specificity of restrictive recognition as well as the appropriate effector function. (7) Proposition: The t-cell receptor is H-2 encoded.The data presented earlier (1, 14) as well as the competing Janeway-Binz-Wigzell dual-recognition model (59) are analyzed.     

Vereine,Gesellschaften, Anstalten

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Vereine,Gesellschaften, Anstalten

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Vereine,Gesellsochaften, Anstalten

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The migration behavior of proparathyroid hormone, parathyroid hormone, and their peptide fragments during gel filtration

The migration behavior of bovine proparathyroid and parathyroid hormones, as well as several hormonal peptide fragments, has been analyzed by gel filtration on thin-layer plates and by column chromatography. The two hormones migrated appreciably faster than was expected for their molecular weights. Their migration rates decreased with increasing pH and approached values more characteristic of their molecular weights at pH 11.0. Migration rates were the same over a concentration range of 2 × 10^?6–0.9 × 10^?3m. These results indicate that parathyroid hormone does not exist in solution as an aggregate at the concentrations used in these experiments. These studies suggest that the two hormones are asymmetrical, unfolded monomers in acid solution which become more folded or globular at alkaline pH values.