| First Author | De Giorgi L | Year | 1993 |
| Journal | Mouse Genome | Volume | 91 |
| Issue | 2 | Pages | 316-317 |
| Mgi Jnum | J:14658 | Mgi Id | MGI:62822 |
| Citation | De Giorgi L, et al. (1993) A superantigen-like expression on BALB/c mice recognized by a murine monoclonal antibody: DG-E12. Mouse Genome 91(2):316-317 |
| abstractText | Full text of Mouse Genome contribution: A SUPER ANTIGEN-LIKE EXPRESSION ON BALB/c MICE RECOGNIZED BY A MURINE MONOCLONAL ANTIBODY: DG-E12. L De Giorgi, BS Dehar, JA Habeshaw; Immunology Department, The Rayne Institute, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH; Tel No: 071 928 9292 Ext 3391/3184; FAX No: 071 620 0450 Research News An heterogeneity has been observed in BALB/c (H-2d, Mlsb) congenic strains of mice (OLAC) in relation to the capacity of their lymphocytes to respond in vitro to the addition of DG-El2 mAb by pro1iferation. DG-El2 mAb appears to recognize a determinant on alloresponsive T cells specific for BALB/c mice only; furthermore it has been described to have a role in immune regulation by modification of graft-versus-host disease (GVHD) in a mouse model (De Giorgi et a1, 1992). The preliminary in vivo and in vitro studies suggest that the heterogeneity of response observed in the adult BALB/c mice may only be an acquired characteristic rather than a genetic phenomenon. Heterogeneity of T cell response has not been observed i n young animals between 3 days and 4 weeks old, since lymphocytes o f young mice are all stimulated (100%) by DG-E12 mAb. In contrast, heterogeneity appeared after 4 weeks and was maintained over the next 6-8 months. We can assume that what is acquired during adult life, in BALB/c mice, is the deletion of T cells showing a specific proliferative response. This characteristic divides BALB/c mice into two groups; a group whose lymphocytes are stimulated in vitro by the mAb DG-E12 (which are called DG-E12+ve) and a group of mice whose lymphocytes are not stimulated by the mAb (DG-E12-ve). It must be therefore a characteristic dependent upon the acquisition of tolerance to an exogenous antigen (ExA), i.e. deletion in animals positive for the (ExA) antigen (DG-E12+ve) recognized thus by the mAb DG-E12. This was confirmed by FACS analysis studies on lymphocytes from (DG-E12+ve) and (DG-E12-ve) BALB/c mice. It was found that CD4+DG-E12+ double positive T cells were reduced in BALB/c (DG-E12+ve) mice from 33% +/- 7.6 to 1.8% +/- 0.2. In contrast the lymphocyte profile of BALB/c mice defined as (DG-E12-ve), expressed high level o f (CD4+DG-E12+) double staining T cells. We postulate that exogenous antigen (ExA) may be involved in the selection process of the T cell repertoire during the maturation period of the immune system. T cells from BALB/c mice expressing the exogenous antigen (ExA) are thus subjected to deletion; therefore in these mice a new T cell receptor repertoire may be developed as an acquired characteristic (DG-El2-ve). In in vitro MLR between responder lymphocytes from BALB/c (DG-E12-ve) and BALB/c (DG-E12+ve) an unidirectional stirnulation has been observed and the stimulation indices (SI) in these combinations ranged between 5 and 11. This MLR reactivity is comparable to that observed between Mls incompatible combinations. In order to establish whether (ExA) antigen is associated to the Mls locus discovered by Festenstein (1966), lymphocytes from Mlsa positive mice of BALB/c background: BALB. D2MA (Festenstein and Berumen, 1983), were tested using the in vitro mitotic effect of the DG-El2 mAb. Our results showed that 1ymphocytes from adult BALB.D2MA mice were not stimulated by DG-El2 mAb in a 3 days culture. We conclude that lymphocytes from BALB/c mice (DG-E12+ve) which are stimulated by the mAb DG-El2 may express on their B cells a super-antigen-like molecule (ExA) which is neither H-2 nor Mls-linked, and is recognized by T lymphocytes of other BALB/c mice (DG-E12-ve). Such mice do not delete double positive CD4+DG-E12+ T cells. The fact that BALB/c (DG-E12-ve) can only respond in an in vitro MLR to BALB/c (DG-E12tve) signifies that the mAb DG-El2 may be against a component of the TCR of BALB/c (DG-E12-ve) relative with the unknown exogenous antigen (ExA). The nature of this antigen is under investigation. We propose (ExA) antigen as a new marker for an alternative murine minor locus or superantigen, which 1ike the Mls locus may have importance in immune regulation and tolerance induction. Further in vivo genetic studies using intercrossing (IC) and backcrossing (BC) between defined matings of different BALB/c mice are in hand. References De Giorgi L, Habeshaw JA and Cazenave PA (1992) Research Immunology 143:863-871. Festenstein H (1966) Ann N Y Acad Sci 129:567-572. Festenstein H and Berumen L (1984) Transplantation 37:322-324. |
