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Affinity, avidity and the E-rosette receptor
Journal oflmmunologicalMethods, 72 (1984) 305-309
305
Elsevier JIM03161
Letters to the Editors Hong Kong, 14 March 1984 Re.:
Affinity, avidity and the E-rosette receptor
Dear Editors, T lymphocytes differ in their ability to form E rosettes with sheep red blood cells (SRBC). Manifestations of these differences include the speed of rosette formation (active versus late), temperature stability (4°C versus 37°C), requirement for protein-enriched medium, and the formation of rosettes at different lymphocyte:SRBC ratios. These phenomena have been explained as expressions of receptor affinities on different T-cell subsets (Taniguchi et al., 1976; Holzman and Lawrence, 1977; West et al., 1977; Pezzutto et al., 1984). By immunological convention, affinity is: 'a thermodynamic expression of the strength of interaction or binding between an antibody combining site and an antigenic determinant, and thus, of the stereochemical compatibility between them' (Herbert and Wilkinson, 1977). It is acceptable to use the term in the context of thermodynamic interaction between sites other than antibody and hapten, but its application to the E rosette is misleading and, therefore, undesirable. Some of the cell-related factors probably affecting E-rosette formation are listed in Table I; variables which do not affect the cell membrane, e.g. lymphocyte:SRBC ratio, are not included. Affinity will certainly affect the speed, stability and other expressions of rosette formation. However it is only one of several interacting factors, and possibly the most difficult to evaluate. The recipient and the target are particulate and complex, precluding direct measurement of the thermodynamic forces between them: studies of solubilized receptors (Chisari et al., 1977) and binding sites are required but the relevance to the forces in operation between whole cells would be difficult to assess. Meanwhile, attributing different technical characteristics of this system to affinity of the E receptor clearly assumes that no other variations are occurring, an assumption with no foundation. Expressions of the outcome of the interaction between complex sites subjected to numerous potential molecular variables are best ascribed to 'avidity' (Herbert and Wilkinson, 1977). It is recommended that in future, as sometimes in the past (Chisholm and Tubergen, 1976), this term should be used to describe the charactertistics of E-rosette formation. This will avoid thermodynamic implications, and emphasise that the rosette is an outcome of numerous intricate variables, not an assay of one.
Department of Pathology University of Hong Kong Hong Kong 0022-1759/84/$03.00 © 1984 Elsevier Science Publishers B.V.
D.A. Higgins
306 TABLE I CELL FACTORS AFFECTING E-ROSETTE FORMATION
Lymphocyte variables 1. Presence of receptors 2. Accessibility of receptors (relationship to cell membrane; stearic hindrance) 3. Affinity of receptors (includes requirement/presence of suitable residues, e.g. sialic acid; thus reflects primary structure) 4. Density of receptors (might alter as cell matures; could vary between subsets) 5. Rate of elution of receptors (might explain rosette breakdown and decay; might be dependent on temperature and metabolic processes) 6. Rate of synthesis of receptors (must exceed rate of elution if stable rosettes are to form; probably affected by temperature and presence of metabolites) 7. Receptor susceptibility to enhancing substances (different T-cell subsets vary in their response to different substances; might be direct physicochemical effects but could be reflections of altered cell metabolism and synthesis) 8. Receptor susceptibility to inhibitors (e.g. chelating agents, rosette-inhibiting factors; could be direct physicochemical inhibition but could be reflections of altered cell metabolism and synthesis) 9. Balance of receptor heterogeneity (one cell, one receptor structure, or do receptors with different characteristics occur on each cell?) Erythrocyte variables 1. Presence of binding sites 2. Accessibility of binding sites "~ (probably affected by treatment with neuraminidase or AET) 3. Affinity of binding sites J 4. Density of binding sites 5. Rate of elution of binding sites (resynthesis unlikely) 6. Balance of heterogeneous binding sites (if they vary) 7. Size of RBCs (larger RBCs will require stronger bond; might explain non-rosetting with other species RBCs but variation will occur between individual sheep, and those of anaemic sheep will certainly be larger)
References Chisari, F.V., W.J. Gealy and T.S. Edgington, 1977, J. lmmunol. 118, 1138. Chisholm, R.L. and D.G. Tubergen, 1976, J. Immunol. 116, 1397. Herbert, W.J. and P.C. Wilkinson, 1977, A Dictionary of Immunology (Blackwell Scientific Publications, Oxford). Holzman, R.S. and H.S. Lawrence, 1977, J. Immunol. 118, 1672. Pezzutto, A., R. Raimondi, G. Semenzato and J. Wybran, 1984, J. lmmunol. Methods 66, 1. Taniguchi, N., N. Okuda, N. Moriya, T. Miyawaki and T. Nagaoki, 1976, Clin. Exp. Immunol, 24, 370. West, W.H., S.M. Payne, J.L. Weese and R.B. Herberman, 1977, J. lmmunol. 119, 548.
305
Elsevier JIM03161
Letters to the Editors Hong Kong, 14 March 1984 Re.:
Affinity, avidity and the E-rosette receptor
Dear Editors, T lymphocytes differ in their ability to form E rosettes with sheep red blood cells (SRBC). Manifestations of these differences include the speed of rosette formation (active versus late), temperature stability (4°C versus 37°C), requirement for protein-enriched medium, and the formation of rosettes at different lymphocyte:SRBC ratios. These phenomena have been explained as expressions of receptor affinities on different T-cell subsets (Taniguchi et al., 1976; Holzman and Lawrence, 1977; West et al., 1977; Pezzutto et al., 1984). By immunological convention, affinity is: 'a thermodynamic expression of the strength of interaction or binding between an antibody combining site and an antigenic determinant, and thus, of the stereochemical compatibility between them' (Herbert and Wilkinson, 1977). It is acceptable to use the term in the context of thermodynamic interaction between sites other than antibody and hapten, but its application to the E rosette is misleading and, therefore, undesirable. Some of the cell-related factors probably affecting E-rosette formation are listed in Table I; variables which do not affect the cell membrane, e.g. lymphocyte:SRBC ratio, are not included. Affinity will certainly affect the speed, stability and other expressions of rosette formation. However it is only one of several interacting factors, and possibly the most difficult to evaluate. The recipient and the target are particulate and complex, precluding direct measurement of the thermodynamic forces between them: studies of solubilized receptors (Chisari et al., 1977) and binding sites are required but the relevance to the forces in operation between whole cells would be difficult to assess. Meanwhile, attributing different technical characteristics of this system to affinity of the E receptor clearly assumes that no other variations are occurring, an assumption with no foundation. Expressions of the outcome of the interaction between complex sites subjected to numerous potential molecular variables are best ascribed to 'avidity' (Herbert and Wilkinson, 1977). It is recommended that in future, as sometimes in the past (Chisholm and Tubergen, 1976), this term should be used to describe the charactertistics of E-rosette formation. This will avoid thermodynamic implications, and emphasise that the rosette is an outcome of numerous intricate variables, not an assay of one.
Department of Pathology University of Hong Kong Hong Kong 0022-1759/84/$03.00 © 1984 Elsevier Science Publishers B.V.
D.A. Higgins
306 TABLE I CELL FACTORS AFFECTING E-ROSETTE FORMATION
Lymphocyte variables 1. Presence of receptors 2. Accessibility of receptors (relationship to cell membrane; stearic hindrance) 3. Affinity of receptors (includes requirement/presence of suitable residues, e.g. sialic acid; thus reflects primary structure) 4. Density of receptors (might alter as cell matures; could vary between subsets) 5. Rate of elution of receptors (might explain rosette breakdown and decay; might be dependent on temperature and metabolic processes) 6. Rate of synthesis of receptors (must exceed rate of elution if stable rosettes are to form; probably affected by temperature and presence of metabolites) 7. Receptor susceptibility to enhancing substances (different T-cell subsets vary in their response to different substances; might be direct physicochemical effects but could be reflections of altered cell metabolism and synthesis) 8. Receptor susceptibility to inhibitors (e.g. chelating agents, rosette-inhibiting factors; could be direct physicochemical inhibition but could be reflections of altered cell metabolism and synthesis) 9. Balance of receptor heterogeneity (one cell, one receptor structure, or do receptors with different characteristics occur on each cell?) Erythrocyte variables 1. Presence of binding sites 2. Accessibility of binding sites "~ (probably affected by treatment with neuraminidase or AET) 3. Affinity of binding sites J 4. Density of binding sites 5. Rate of elution of binding sites (resynthesis unlikely) 6. Balance of heterogeneous binding sites (if they vary) 7. Size of RBCs (larger RBCs will require stronger bond; might explain non-rosetting with other species RBCs but variation will occur between individual sheep, and those of anaemic sheep will certainly be larger)
References Chisari, F.V., W.J. Gealy and T.S. Edgington, 1977, J. lmmunol. 118, 1138. Chisholm, R.L. and D.G. Tubergen, 1976, J. Immunol. 116, 1397. Herbert, W.J. and P.C. Wilkinson, 1977, A Dictionary of Immunology (Blackwell Scientific Publications, Oxford). Holzman, R.S. and H.S. Lawrence, 1977, J. Immunol. 118, 1672. Pezzutto, A., R. Raimondi, G. Semenzato and J. Wybran, 1984, J. lmmunol. Methods 66, 1. Taniguchi, N., N. Okuda, N. Moriya, T. Miyawaki and T. Nagaoki, 1976, Clin. Exp. Immunol, 24, 370. West, W.H., S.M. Payne, J.L. Weese and R.B. Herberman, 1977, J. lmmunol. 119, 548.