The Elusive T Cell Receptor

The relationship between H-2 complex-associated determinants, Fc receptors, and specific antigen-recognition sites on T and B cells was examined by binding and functional assays. The Fc receptor was detected by radiolabeled immune complexes or aggregated human IgG. Both these reagents selectively bound to B cells, not to T cells. When spleen cells, from mice primed to several antigens, were exposed to highly substituted radioactive aggregates, their capacity to transfer both a direct and indirect plaque-forming cell response to these antigens was abrogated. Addition of B cells, but not of T cells, restored responsiveness. Complexed Ig binding to Fc receptors was prevented by pretreatment of mixed lymphoid cell populations with antisera directed against membrane components on the same cell (e.g., H-2) and on other cells (e.g., theta). The lack of specificity of inhibition was thought to be due to the formation on cell surfaces of antigen-antibody complexes which would then attach to the Fc receptor during the incubation precedure. Specific blockade of the Fc receptor during the incubation procedure. Specific blockade of the Fc receptor however occurred when B cells were pretreated with the Fab fragments of anti-H-2 antibody. This was demonstrated autoradiographically and by inhibition of aggregate-induced suicide. The blocking activity of ante-H-2 Fab was removed by absorption with spleen cells from thymectomized irradiated mice but not with thymus cells of appropriate specificity. This suggested that the antibodies involved had specificity for determinants on the B-cell membrane distinct from those coded by the K or D end of the H-2 complex, and either absent from, or poorly represented on, thymus cells. Specific antigen-induced suicide of B cells was achieved simply by incubating the cells with radioactive antigen in the cold. T-cell suicide on the other hand required that the 125I-labeled antigen be presented to the T cells at 37 degrees-C on the surface of spleen cells from antigen-primed mice. Pretreatment of T cells with the Fab fragment of anti-H-2 antibody protected them from the suicide effect. By contrast no such protection of B cells could be achieved by this procedure. In other words H-2 (? Ir)-associated determinants may not only be in close proximity to the antigen-binding site on T cells but, in addition, may be involved in the effective operation of the receptor.

Section: Effect Of Pretreatment Withmentioning

confidence: 99%

Relationship between Fc receptors, antigen-binding sites on T and B cells, and H-2 complex-associated determinants.

Basten¹,

Miller²,

Abraham³

1975

“…Such receptors on mouse B cells are basically conventional immunoglobulins coded for by genes located on chromosomes 12 (heavy chain), 6 (kappa chain), and 9, 13, or 16 (lambda chain) (5-7). The antigen-specific receptor on T cells is considered elusive (8). The mystery of this receptor has been elucidated by the finding that anti-idiotypic antisera react both with specific antibodies and with specific T cells (9,10), and that the idiotypes are localized on antigen-specific receptors on T lymphocytes.…”

mentioning

confidence: 99%

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

Binz¹,

Wigzell²

1981

Antisera specific for the constant part Ctau of T cell receptor molecules in mice and rats have been produced in rabbits by immunization with idiotype-positive rat T cell molecules. Such antisera could be shown to react with the majority of normal T lymphocytes from both rats and mice. Mixed leukocyte culture-activated T blasts displayed a higher percentage of positive cells than concanovalin A- or phytohemaglutinin-induced T blasts. Lipopolysaccharide-induced B blasts were not reactive with the antiserum. Lyt-1-,2+,3+ blasts displayed a significantly brighter straining than the corresponding Lyt-1+,2-,3- blasts. Isolation of the reactive molecules from T cells by immunosorption yielded a 70,000-dalton single chain polypeptide as the dominant group of molecules. Plasmin caused the chain to split into 45,000- and 25,000-dalton polypeptides, with the smaller fragment displaying antigen-binding capacity. Molecules identical in size and plasma degradation patterns were isolated from Lyt-1+,2-3- and 1-,2+,3+ blasts. Preliminary functional data supported the view that the antiserum is directed against the constant region Ctau relevant receptor structures on immunocompetent T lymphocytes.

“…Although no direct cytotoxic effect of antiallotypic antibodies has been demonstrated (26-28), Mage (2) has recently discussed alternative mechanisms by which prolonged exposure to such antibodies might lead to eventual cell inactivation or death. A number of investigators have studied the ability of antibodies directed against membrane-bound antigens to interfere with the activity of such cells in the graft-vs .-host or the mixed lymphocyte reactions (29)(30)(31)(32)(33)(34) . Where tested, the antisera used were shown not to be cytotoxic.…”

Section: Discussionmentioning

confidence: 99%

In vitro studies on allotype suppression. III. compounds of antiallyotype serum active in release from allotype suppression.

Alder¹,

Adler²

1975

Spleen cells of b4b6 rabbits, shown to be deficient in their ability to produce b4Ig due to prenatal exposure to anti-b4, formed anti-T2 antibodies marked with the b4 determinant in response to solubilized T2 phage (S-T2) only when cultured in the presence of antibodies specific for the nonsuppressed type (b6), thus confirming and extending the previously reported observation of release from b4 suppression in cultured cells of b4-suppressed b4b5 rabbits treated with anti-b5 serum. Only antiallotype sera made in b4 rabbits were active in reversing b4 suppression. Anti-b5 or anti-b6 sera from rabbits of allotypes b6 or b5, respectively, when used in concentrations which completely or partially inhibited the formation of anti-T2 antibodies marked with the corresponding nonsuppressed allotype of the spleen donor, proved to be almost completely ineffective in causing release of suppression. Exceptions were noted when spleen cells of rabbits advanced in spontaneous escape from suppression were tested with such sera. The addition of normal b4 serum to non-b4 antiallotypic sera rendered them as effective in releasing b4 suppression in vitro as were antisera from b4 rabbits. Furthermore, the capacity of a b4 antiallotype serum to cause reversal of b4 suppression could be potentiated by the addition of normal b4 serum, indicating that nonantibody b4 Ig is a limiting factor in such a serum. Thus, the release from allotype suppression observed in cultures of spleen cells from b4-suppressed heterozygous rabbits is dependent upon the presence of two components: antibodies directed against the nonsuppressed allotype of the donor and normal b4Ig. These findings are interpreted in terms of alternate hypotheses involving (a) a mechanism of b4 derepression and (b) inactivation of a suppressor cell with recognition for a b4-labeled target.