The Frequency of Antigen-Sensitive Cells in Tissue Transplantation

Abstract

One of the obvious ways of testing the clonal selection hypothesis is to determine the minimum number of cells needed to initiate a measurable immune response. At least in the uncompromising, and now classical, hypothesis of one antigen-sensitive cell clone per antibody specificity (1, 2) it is mandatory that a given antigenic determinant should not be recognizable by every small lymphocyte--accepting that antigen-sensitive ceils are to be found among this, in several ways, heterogenous cell population. While this extreme result, if found, would truly invalidate the hypothesis it is unfortunately not possible to define exactly the maximum frequency of antigen-sensitive cells which would still be compatible with the hypothesis. Clearly, the more complex the immunological universe is thought to be, the higher becomes the number of different clones required by the hypothesis, and the lower becomes the expected frequency of a cell belonging to one particular clone. Few immunologists would probably expect a frequency higher than 10 -4.For reasons which were suggested by earlier studies of the factor of immunization (3), the strong histocompatibility antigens were considered to provide a particularly exacting test of the clonal selection hypothesis. The graftvs.-host (GVH) reactions in chicken embryos injected intravenously with adult chicken lymphocytes were used in the present study to determine the frequency of antigen-sensitive cells with re3pect to the strong antigens of the B locus (4). It is concluded that their frequency is too high to be compatible with the orthodox version of clonal selection.

T cell receptors with allo-major histocompatibility complex specificity from rat and mouse. Similarity of size, plasmin susceptibility, and localization of antigen-binding region.

“…With regard to the latter parameter, T lymphocytes are known to be obsessed with reactivity toward MHC antigens (40)(41)(42), and both helper and killer T cells frequently "see" antigen in the context of their own MHC structures in a manner quite distinct from B lymphocytes (43). The molecular details underlying the antigen-binding receptors of T cells are still confusing.…”

A simple and effective method for cancer immunotherapy by inactivated allogeneic leukocytes infusion

“…virus proteins) are about 1/10 4 or 1/10 5 , 1-10% of an individual's T lymphocytes will respond to the allogeneic MHC molecules of another individual. 23 A recent study put this value at 7%. 24 The molecular mechanism of this phenomenon is uncertain, 25 but it distinctly involves a direct activation of T cells by intact allogeneic MHC molecules on the surface of allogeneic professional APCs [for example, dendritic cells (DCs)].…”

Specific Positive Selection of Lymphocytes Reactive to Strong Histocompatibility Antigens

“…It is not at present possible to decide what the basis for this cross-reaction may be but in any event it seems to dispose of total exclusiveness among cells reactive to different major H antigens as suggested by Ford and Atkins (8) and thus reduces to some extent the threatened "over occupancy" of the T-cell pool by cells reactive to major H antigens. This concern arose because of the repeated finding that the frequency of reactive to a given H alloantigen was very high (1-12 % according to various estimates [1][2][3]21]), so that reactivity at that frequency to all alloantigens of the species would require the commitment of more T cells than any individual possessed. An unanswered but crucial question is whether cells selected on the basis of reactivity to a major H alloantigen also include populations reactive to determinants of conventional antigens.…”