Inherited polymorphism of the human T-cell antigen receptor detected by a monoclonal antibody.

Abstract

Three different murine monoclonal antibodies to the human clonotypic T-cell antigen receptor (l) immunoprecipitate the -sp chain heterodimer; (it) induce comodulation of the clonotypic molecule with the T3 molecular complex; (iiW) stain small populations of normal polyclonal T cells, suggesting that they react with variable or joining region determinants of the clonotypic receptor; and (iv) induce proliferation of resting T cells. While two of these antibodies detect the clonotypic receptor in all individuals studied, the third antibody (OT145), described herein, does not detect the T-cell antigen receptor on T cells of all individuals. By indirect immunofluorescence, three groups can be distinguished within a population of individuals (n = 138) by OT145. The antigen receptor of T lymphocytes may be classified as a member of a large family of related molecules, the immunoglobulin supergene family (1). Several members of this supergene family display genetically transmitted polymorphisms. For example, using antibodies as a probe, early investigators detected allelic forms of immunoglobulin chains, termed allotypes (2, 3). Allotypic systems have been described on both the constant and variable (V) portions of immunoglobulin heavy chains and on constant portions of light chains (4-6). Allotypes are inherited in an autosomal codominant manner. In view of the remarkable structural similarities between the T-cell antigen receptor and immunoglobulins, it is reasonable to expect that allotypic determinants will be identified on the a and/or 83 chains of the T-cell antigen receptor. Recent studies have used restrictionfragment-length polymorphism (RFLP) to identify polymorphisms in the human a and 8 chain genes (7,8). While these RFLPs map to introns of both genes, similar polymorphisms of the exons, which could result in amino acid sequence differences responsible for the expression of allotypic determinants, have not yet been described.Our group and others have raised monoclonal antibodies (mAbs) against the T-cell antigen receptor, some of which react with small subsets of normal human T cells (9-13). In one case the determinant recognized by this type of mAb was found to be a 13 chain V region determinant (12). We have characterized the small subsets of peripheral blood T cells identified by two such mAbs, designated S511 and C37 (10, 11). In both cases S511-and C37-reactive (S511' and C37+) T cells may belong to either the T4' or T8' subset of T cells.In both cases the mAbs can be used as mitogens to selectively expand these small populations of T cells and derive interleukin 2-dependent polyclonal and cloned S511' or C37' T-cell lines (refs. 10 and 11; unpublished data

T cell antigen receptor V gene usage. Increases in V beta 8+ T cells in Crohn's disease.

“…In general, the percentages of Ti3a+ cells remained constant, as also described with other Vft-specific MAbs in previous studies (4,5). How-ever, there were some exceptions.…”

“…A growing number ofMAbs to human TCR V region products are being carefully characterized with respect to their specificity for various V gene products (4,5,9,11,12,18,19). These MAbs are useful tools to determine V gene usage by T cells in different tissue sites.…”

“…The MAbs listed in Table I have been described in detail (4,(7)(8)(9) (14). The probe used corresponds to the V region of YT35: basepairs 100-430 of the published sequence (15).…”

“…As such they serve as useful tools to analyze VPl gene usage by T cells in the blood or in tissue sections. In prior studies we used three such MAbs to determine V gene usage in normal donors (4) and in patients with autoimmune disorders (5). No disease-related changes in V gene usage were detected.…”

Helper T cell-dependent human B cell differentiation mediated by a mycoplasmal superantigen bridge.

“…We noted a strong negative correlation between MAM-reactive T cells and T cells expressing TCR V-0 5 gene products recognized by mAb C37 (9), and V a 6.7 recognized by mAb OT145 (10). To prove that MAM-dependent B cell activation requires superantigen-specific Th cells, CD4' TCL were obtained from cultures of PBL stimulated with either MAM or the mAb C37.…”