Immunology Today June 1982
Transplantation
Receptors, antibodies and disease
Applied wisdom
from J o h n N e w s o m - D a v i s and A n g e l a V i n c e n t Biochemists, endocrinologists, immunologists and neurologists share an interest in cell surface receptors, as was cvidcnt at a recent symposium held by the Ciba Foundation*. When these receptors are targets [or at.ttoantibodies, endocrine or neurological disease can result. Attention focussed particularly on receptors (R) for thyroid stimulating hormone (TSH), insulin, acetylcholinc (ACh), prolactin and [32-adrenergic agonists. The clinical importance of autoantibodies to receptors, judged purely in nurnerical terms, varies considerably. Insulin-resistant diabetes (insulin-R antibody), for example, is extremely rare - less than 50 cases * Receptors Antibodies and Disease (Ciba Symposium no. 90) was organized by I)r David Evered and (:haired by Professor N. A. Mitchison. The proceedings will bc published by Pitman Medical Ltd.
have been reported worldwide, to date. ()n the other hand Graves' disease (TSI I-R antibody) and myasthenia gravis (ACh-R antibody) are moderately prevalenl while asthma and other atopic disorders ([3e-adrenergic-R antibody) are very common. Direct implication of the relevant antibodies in the disease process scems well established for most of the disorders discussed, although some uncertainty exists aboul lhe role of the recently identified [%-adrenergic-R antibody. In asthma a reduction in lung tissue ,ge adrenergic receptors, as measured by agonist binding or !3e responses, has been established for some time and antibodies specific [or the [32 receptor can be identified either by' inhibition of agonist binding, by immunoprecipitation of solubilized /70
2. Insulin-R
1. AChR
3. Prolactin -R
,.rllmm.d ,m p
4, 8 2- adrenergic- R
,5 TSH- R
Fig. 1. Diagrammatic representation (roughly to scale) of proposed subunit structures of the principal receptors discussed, indicating the size and number of binding site(s) for the natural ligand (hatched). P,eceptnrs are ranked (1-5) according to the information available. Numbers denote the rnol. wt.
from E l i z a b e t h S i m p s o n T h e t r a d i t i o n of a n a n n u a l " R o u n d T a b l e
Symposium on Applied Immunology' was carried into its 13th year in Axams, Austria, on 25-27 ,January. ()n these occasions small numbers of clinicians and scientists meet to discuss new developments in researcb that have mutual interest. In the opening session on cellsurface antigens H. Bather (Riisvijk) discussecl the itt-me', effect of monuclonal antibodies (MAbs) directed against '['-cell subsets in Rhesus monkeys grafted with alh)geneic skin. The MAbs defined human lymphocyte subsets that erossreaet with the equivalent rhesus monkey cells. Antibodies against tile helper/inducer subset (OKT4 equivalent) prohmged skin allograft survival whereas those directed against the cylotoxie/suppresser subset (()KT8 equivalent) not only failed to prolong surviwd but may have shortened it. These resuhs at'(" in line with recenl reports that in mite and rats the T cells involved in initiating graft rejection are of the helper (Lyl + ) phenotype and not the tyrotoxic/suppressor (l.yl+ ~ ) i~heno-. type. 1). Arndt-Jovin ((;6ttingen) presented her use of sophisticated physical methods (fluorescence energy transfer, rotational diffusion and translational diffusion) to assess the density, proximity and mobility of mouse• II-2 ( Kk) antigens delected with monoclonal antibodies. The basic information obtained fi'oni ll~ese studies should alloy, direct examination of how tt-2 antigens 'assoeiate' with such extrinsic antigens as viruses and thus tbe necessary eunsh'aints ful considering l l~c ahered self versus dual receptor hypothesis of T-ceil re¢et> tors. P. Peterson (Uppsala) ln'esentcd
Transplantation
Receptors, antibodies and disease
Applied wisdom
from J o h n N e w s o m - D a v i s and A n g e l a V i n c e n t Biochemists, endocrinologists, immunologists and neurologists share an interest in cell surface receptors, as was cvidcnt at a recent symposium held by the Ciba Foundation*. When these receptors are targets [or at.ttoantibodies, endocrine or neurological disease can result. Attention focussed particularly on receptors (R) for thyroid stimulating hormone (TSH), insulin, acetylcholinc (ACh), prolactin and [32-adrenergic agonists. The clinical importance of autoantibodies to receptors, judged purely in nurnerical terms, varies considerably. Insulin-resistant diabetes (insulin-R antibody), for example, is extremely rare - less than 50 cases * Receptors Antibodies and Disease (Ciba Symposium no. 90) was organized by I)r David Evered and (:haired by Professor N. A. Mitchison. The proceedings will bc published by Pitman Medical Ltd.
have been reported worldwide, to date. ()n the other hand Graves' disease (TSI I-R antibody) and myasthenia gravis (ACh-R antibody) are moderately prevalenl while asthma and other atopic disorders ([3e-adrenergic-R antibody) are very common. Direct implication of the relevant antibodies in the disease process scems well established for most of the disorders discussed, although some uncertainty exists aboul lhe role of the recently identified [%-adrenergic-R antibody. In asthma a reduction in lung tissue ,ge adrenergic receptors, as measured by agonist binding or !3e responses, has been established for some time and antibodies specific [or the [32 receptor can be identified either by' inhibition of agonist binding, by immunoprecipitation of solubilized /70
2. Insulin-R
1. AChR
3. Prolactin -R
,.rllmm.d ,m p
4, 8 2- adrenergic- R
,5 TSH- R
Fig. 1. Diagrammatic representation (roughly to scale) of proposed subunit structures of the principal receptors discussed, indicating the size and number of binding site(s) for the natural ligand (hatched). P,eceptnrs are ranked (1-5) according to the information available. Numbers denote the rnol. wt.
from E l i z a b e t h S i m p s o n T h e t r a d i t i o n of a n a n n u a l " R o u n d T a b l e
Symposium on Applied Immunology' was carried into its 13th year in Axams, Austria, on 25-27 ,January. ()n these occasions small numbers of clinicians and scientists meet to discuss new developments in researcb that have mutual interest. In the opening session on cellsurface antigens H. Bather (Riisvijk) discussecl the itt-me', effect of monuclonal antibodies (MAbs) directed against '['-cell subsets in Rhesus monkeys grafted with alh)geneic skin. The MAbs defined human lymphocyte subsets that erossreaet with the equivalent rhesus monkey cells. Antibodies against tile helper/inducer subset (OKT4 equivalent) prohmged skin allograft survival whereas those directed against the cylotoxie/suppresser subset (()KT8 equivalent) not only failed to prolong surviwd but may have shortened it. These resuhs at'(" in line with recenl reports that in mite and rats the T cells involved in initiating graft rejection are of the helper (Lyl + ) phenotype and not the tyrotoxic/suppressor (l.yl+ ~ ) i~heno-. type. 1). Arndt-Jovin ((;6ttingen) presented her use of sophisticated physical methods (fluorescence energy transfer, rotational diffusion and translational diffusion) to assess the density, proximity and mobility of mouse• II-2 ( Kk) antigens delected with monoclonal antibodies. The basic information obtained fi'oni ll~ese studies should alloy, direct examination of how tt-2 antigens 'assoeiate' with such extrinsic antigens as viruses and thus tbe necessary eunsh'aints ful considering l l~c ahered self versus dual receptor hypothesis of T-ceil re¢et> tors. P. Peterson (Uppsala) ln'esentcd
