Specificity and heterogeneity of helper T cells in the response to serum albumins in mice
Authors: Rajewsky K. , Mohr R. 
Published: February 2007

The object of the present study was to compare the fine specificity of helper T cell receptors to that of humoral antibodies, the combining sites of which are presumed to represent replicas of antibody‐forming cell precursor (AFCP) receptor combining sites.

The main elements of our experimental system were a series of cross‐reacting serum albumins coupled to the 4‐hydroxy‐5‐iodo‐3‐nitrophenacetyl (NIP) hapten and a cell transfer system, in which albumin‐specific helper cells mediate the secondary anti‐hapten response of hapten‐primed AFCP to hapten‐albumin conjugate. Dose response analyses showed that the response in the transfer system was limited by two components only.

Two experimental approaches, independent of each other, are described in this paper. The first consisted of establishing serological cross‐reaction patterns in the albumin system by an extensive analysis in radioactive binding assays and comparing this pattern to the cross‐stimulation pattern, which was obtained by determining helper activity of albumin‐primed helper cells towards hapten conjugates of the various cross‐reacting albumins in the cell transfer system. Since native serum albumins are particularly stable proteins, which possess similar physicochemical properties and can be expected to behave similarly in the body, the cross‐stimulation patterns reflect, in all likelihood, cross‐reactions at the level of the helper cell receptors.

A possible interference of circulating anti‐albumin antibody with the specificity of cross‐stimulation was excluded in experiments in which column‐purified helper T cells were used. This was corroborated by the paralysis experiments summarized below.

In a second approach aimed at comparing the heterogeneity in helper and AFCP receptors, anti‐albumin antibodies and helper cells were classified into subpopulations of defined specificities. Immunosorbent techniques were used for this purpose at the level of the antibodies, and paralysis experiments for the classification of helper cells. In this system, in contrast to the first approach, we assess the specificity distribution in unprimed T helper cells.

A consistent picture emerged from the two experimental approaches. The discriminating power of the receptor system in primed and unprimed T helper cells was similar and of a high order, and a striking similarity to antibody specificity, in particular to that of highly avid antibody, was observed. Two cases of asymmetrical serological cross‐reactions repeated at the level of the helper cells. The data strongly support the concept that AFCP and T helper cells express the same system of antigen‐binding receptors.

In addition, the experiments provide clear examples of how the distribution of receptor specificities can be selectively modulated in the helper cell population during ontogeny. Whereas in a normal mouse, bovine serum albumin (BSA) and sheep serum albumin cross‐react strongly at the levels of both T helper and B cell receptors, in an animal low zone tolerant to BSA, this cross‐reaction disappears selectively in the T cell compartment.

This result shows that when differences in the specificity of T and B cell recognition are encountered, this does not necessarily imply receptors of a different nature on the two cell types. It also excludes the possibility that helper cell receptors are passively adsorbed, conventional humoral antibody.