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Immunogenetics and rheumatoid arthritis
Immunology Today, Vol. 9, No. 5, 1988
Immunogeneticsand rheumatoidarthritis
Carboxypeptidase B Treated
-ISir, Recently, D.M. Grennan stated that "current technology for C4 allotyping demands family studies for confident identification of variants" (Immunol. Today, 1987, 9, 33-34). A 6 , ~ However, I would like to draw your A3 ,, readers' attention to a published method for C4 typing which involves treatment of plasma samples with carboxypeptidase B before treat- B 1 - - - - ment with neuraminidase (Fig. 1)1. The benefit of the method is in simplification of the typing pattern, with heterozygous null alleles showing as less intense bands. The reason that l 1 2 3 4 5 6 7 8 9 10 particularly wish to draw readers' Fig. 1. Effects of carboxypeptidase B on pattern of C4 after agarose gel electrophoresis of EDTA-plasma. attention to this method is that C4 Tracks 1 and 6, pooledaged(20°C,4°C)plasma:all other tracks,freshfrozenplasmafrom individuals. typing need no longer be regarded Tracks 1 and6, C4A3,B1; tracks2 and 7, C4AQO,B1; tracks3 and S, C4A6,A3, B1, BQO;tracks4 and g, as a specialist art and could be car- C4A3,BI; tracksSand 10, C4A3,BQO. ried out by routine tissue typing All samples, either with or without carboxypeptidasetreatment, were subsequentlyincubated with laboratories. Results published by neuraminidasebeforee/ectrophoresis(fordetailsseeRef. 1).(PublishedwithpermissionfromBiochem.J.239, Alper and colleagues 2 suggest that p. 764~ 1986TheBiochemicalSociety,London.) HLA typing in the class I, II and III References Edith Sire regions would increase the success 1 sire, E. and Cross,53 (1986) rate of transplanted organs. I hope 8iochem. J. 239, 763-767 Department of Pharmacology, University of Fig. 1 will encourage tissue typing 2 Awdeh, Z.L., Alper, C.A., Eynen,E. et Oxford,South Parks Road, Oxford OX1 3QT, ........ laboratories to carry out C4 typing. al. (1985) Lancet ii, 853-855 UK.
DO ~~v-nr hA n r / '~n~u qhR m n n n , , . I n e I~fAIIImlnA * vm mmmvm~t.,um~p j/mvYnu~;
,regulatory signal in T-cell activation? Nearly 20 years after the discovery of CD8 molecules on thymus-derived lymphocytes 1, the function of the CD4 and CD8 molecules on T cells and their role in T-cell activation is still a matter of debate. Several contradictory models have been developed within the past three years. In ~his article, Bernhard Fleischer and Hubert Schrezenmeier discuss recent findings which indicate that the function of these molecules is much more complex than previously appreciated.
Expression of CD4 or CD8 glycoproteins separates most mature T lymphocytes into mutually exclusive subsets. At the clonal level, most T-cell clones expressing the CD4 molecule are specific for class I1 MHC (major histocompatibility complex) antigens, whereas most CD8 ÷ T cells are specific for class I MHC antigens2-4. Since anti-CD4 (Ref. 5) and anti-CD8 (Ref. 6) antibodies can block conjugate formation between target cells and cytotoxic T cells (CTL), it has been assumed that these molecules
132
Department of Medical Microbiology and Immunology, University of UIm, D-7900 UIm, FRG; 1currently at the Department of Medicine, Universityof Mainz, D-6500 Mainz, FRG.
Bernhard FleischerI and Hubert Schrezenmder serve as associative recognition elements that may bind to the nonpolymorphic parts of class II or class I MHC antigens7. Indeed, direct evidence for this binding function is the recent finding 8 that CD4-transfected cells expressing high concentrations of CD4 specifically bind cells bearing HLA class II. T-cell clones vary in their susceptibility to inhibition by anti-CD4 or anti-CD8 antibodies9. At present this is explained by the assumption that resistant T cells express high affinity antigen receptors that make an additional adhesion unnecessarys.9,1o. Consistent with this view is the finding that some CTL-target conjugates can be dissociated by anti-CD4 antibodies. This dissociation is accomplished much more easily with CTL clones inhibitable by anti-CD4 than with CTL clones that cannot be blocked s. Similarly, exceptions to the rule that CD8 + CTL are specific for class I and CD4 ÷ CTL for class II HLA antigens have been explained by high affinity !=inding via the T-cell receptor for antigen (TCR) that does not require additional adhesion 4,9-11. From these findings, (~ 1988, ElsevierPublications,Cambridge 0167 - 4919/88/$02,00
Immunogeneticsand rheumatoidarthritis
Carboxypeptidase B Treated
-ISir, Recently, D.M. Grennan stated that "current technology for C4 allotyping demands family studies for confident identification of variants" (Immunol. Today, 1987, 9, 33-34). A 6 , ~ However, I would like to draw your A3 ,, readers' attention to a published method for C4 typing which involves treatment of plasma samples with carboxypeptidase B before treat- B 1 - - - - ment with neuraminidase (Fig. 1)1. The benefit of the method is in simplification of the typing pattern, with heterozygous null alleles showing as less intense bands. The reason that l 1 2 3 4 5 6 7 8 9 10 particularly wish to draw readers' Fig. 1. Effects of carboxypeptidase B on pattern of C4 after agarose gel electrophoresis of EDTA-plasma. attention to this method is that C4 Tracks 1 and 6, pooledaged(20°C,4°C)plasma:all other tracks,freshfrozenplasmafrom individuals. typing need no longer be regarded Tracks 1 and6, C4A3,B1; tracks2 and 7, C4AQO,B1; tracks3 and S, C4A6,A3, B1, BQO;tracks4 and g, as a specialist art and could be car- C4A3,BI; tracksSand 10, C4A3,BQO. ried out by routine tissue typing All samples, either with or without carboxypeptidasetreatment, were subsequentlyincubated with laboratories. Results published by neuraminidasebeforee/ectrophoresis(fordetailsseeRef. 1).(PublishedwithpermissionfromBiochem.J.239, Alper and colleagues 2 suggest that p. 764~ 1986TheBiochemicalSociety,London.) HLA typing in the class I, II and III References Edith Sire regions would increase the success 1 sire, E. and Cross,53 (1986) rate of transplanted organs. I hope 8iochem. J. 239, 763-767 Department of Pharmacology, University of Fig. 1 will encourage tissue typing 2 Awdeh, Z.L., Alper, C.A., Eynen,E. et Oxford,South Parks Road, Oxford OX1 3QT, ........ laboratories to carry out C4 typing. al. (1985) Lancet ii, 853-855 UK.
DO ~~v-nr hA n r / '~n~u qhR m n n n , , . I n e I~fAIIImlnA * vm mmmvm~t.,um~p j/mvYnu~;
,regulatory signal in T-cell activation? Nearly 20 years after the discovery of CD8 molecules on thymus-derived lymphocytes 1, the function of the CD4 and CD8 molecules on T cells and their role in T-cell activation is still a matter of debate. Several contradictory models have been developed within the past three years. In ~his article, Bernhard Fleischer and Hubert Schrezenmeier discuss recent findings which indicate that the function of these molecules is much more complex than previously appreciated.
Expression of CD4 or CD8 glycoproteins separates most mature T lymphocytes into mutually exclusive subsets. At the clonal level, most T-cell clones expressing the CD4 molecule are specific for class I1 MHC (major histocompatibility complex) antigens, whereas most CD8 ÷ T cells are specific for class I MHC antigens2-4. Since anti-CD4 (Ref. 5) and anti-CD8 (Ref. 6) antibodies can block conjugate formation between target cells and cytotoxic T cells (CTL), it has been assumed that these molecules
132
Department of Medical Microbiology and Immunology, University of UIm, D-7900 UIm, FRG; 1currently at the Department of Medicine, Universityof Mainz, D-6500 Mainz, FRG.
Bernhard FleischerI and Hubert Schrezenmder serve as associative recognition elements that may bind to the nonpolymorphic parts of class II or class I MHC antigens7. Indeed, direct evidence for this binding function is the recent finding 8 that CD4-transfected cells expressing high concentrations of CD4 specifically bind cells bearing HLA class II. T-cell clones vary in their susceptibility to inhibition by anti-CD4 or anti-CD8 antibodies9. At present this is explained by the assumption that resistant T cells express high affinity antigen receptors that make an additional adhesion unnecessarys.9,1o. Consistent with this view is the finding that some CTL-target conjugates can be dissociated by anti-CD4 antibodies. This dissociation is accomplished much more easily with CTL clones inhibitable by anti-CD4 than with CTL clones that cannot be blocked s. Similarly, exceptions to the rule that CD8 + CTL are specific for class I and CD4 ÷ CTL for class II HLA antigens have been explained by high affinity !=inding via the T-cell receptor for antigen (TCR) that does not require additional adhesion 4,9-11. From these findings, (~ 1988, ElsevierPublications,Cambridge 0167 - 4919/88/$02,00