Nomenclature for synthetic peptides representative of immunoglobulin chain sequences. WHO-IUIS Nomenclature Sub-Committee.

Terminology/Terminologie Nomenclature for synthetic peptides representative of immunoglobulin chain sequences* WHO-IUIS Nomenclature Sub-Committee1 The source (species of origin), type, and subgroup (where applicable) of the immunoglobulin chain are indicated prior to the numbers of the first and last amino acid residues comprising the synthesized sequence (stated in parentheses), e.g., human y, (289-298) or rat - (143-147). Square brackets indicate that the peptide is an analogue; substituted amino acids are identified by the three-letter code; superscripted numbers indicating the residue at which the substitution, removal or addition occurs. Further substitutions are specified within round brackets. For example, human y, (289- 298) [D-Thrm¶] and human y, (289-298) [Asn (CHO)f9J. Background Current interest in immunologically active peptides is by no means confined to analogues of thymic hor- mones or complement components; nor to those short-chain peptides which have been shown to pos- sess granulocyte chemotactic activity. In recent years, there has been growing interest in the application of protein synthesis as an alternative strategy to pro- teolytic and chemical fragmentation in the location and characterization of immunoglobulins (as discus- sed, for instance, by Stanworth (16)). Furthermore, this is leading, in many cases, to the development of potentially therapeutic peptides with important immunomodulatory properties. The forerunner of these developments was the synthesis of tuftsin (Thr- Lys-Pro-Arg), representative of a tetrapeptide sequence within the CH2 domains of human IgG (13), which was shown to possess phagocytosis-stimulat- ing activity. Since then, short-chain linear peptides with *This article was drafted by a group of experts working under the auspices of the International Union of Immunological Societies (IUIS) and has been approved by the Nomenclature Committee of the IUIS. Members of the group were D.R. Stanworth (Chairman), K.J. Dorrington, T.E. Hugli, K. Reid and M.W. Turner. A French translation appears on pages 112-114. Requests for reprints and all correspondence should be addressed to the Chairman of the IUIS Nomenclature Committee, Dr M.D. Kazatchkine, Unite d'immuno- pathologie, H6pital Broussais, 96 rue Didot, 75014 Paris, France. Reprint No. 5052 sequences representative of other putative immuno- globulin Fc effector sites have been synthesized and studied; for instance, peptides capable of inhibiting the binding by IgG of Clq (1,10), the binding of IgG to Fc receptors on monocytes and macrophages (3,14), and the action of IgG antibody in ADCC (antibody-dependent cellular cytotoxicity) (5) and NK (natural killer cell) activity (6). The synthetic peptide approach has also been exploited extensively in attempts to identify both mast cell Fc receptor-binding sites (7,17) and trigger sites (16,17). More recently, antibodies raised against peptides have been used as IgE structural probes (e.g., Burt et al. (2)); and immunoglobulin peptides produced by DNA recombinant technology have been employed in similar types of investigation (e.g., Helm et al. (8), Duncan & Winter (4)). Furthermore, synthetic peptides representative of both CH2 and CH3 domain sequences within human IgG have been shown to provide a direct activating signal to resting human B lymphocytes and to enhance antibody production in vitro and in vivo (15), as well as to induce immunoglobulin synthesis by murine B cells (9,12). It is against this background that it is considered timely to establish a nomenclature for synthetic pep- tides representative of imunoglobulin heavy and light chain sequences that is acceptable to investigators working in this field and which will facilitate com- munication and discussion. In the preparation of the following peptide nomenclature proposals, it was considered most important (in view of the tendency Bulletin of the World Health Organization, 66 (1): 109-111 (1990) © World Health Organization 1990 109 WHO-IUIS Nomenclature Sub-Committee of different laboratories to use a different immuno- globulin amino acid numbering system) to refer to a standard source for information about the detailed primary structures of immunoglobulin polypeptide chains; it is suggested that this source should be Sequences of proteins of immunological interest edited by Elvin A. Kabat and colleagues. The 4th edition was published by the U.S. Elvin A. Kabat and colleagues. The 4th edition was published by the U.S. Department of Health and Human Services in 1987. Nomenclature for synthetic peptides Human Immunoglobulin heavy or light chain sequences Where a peptide has been assigned a name, e.g., tuftsin (comprising residues 289-301 of the human Yi chain) or rigin (comprising residues 345-349 of the same chain), it would be expected that it would be referred to in this way in the rest of an article. Otherwise, it is suggested that a nomenclature be adopted which is consistent with that applied to other types of peptide, e.g., hormones. Thus, the source, type and subgroup (where applicable) of the immunoglobulin chain will be indicated prior to the numbers of the first and last amino acid residues comprising the synthesized sequence (stated in paren- theses), e.g., human y, (289-298), rat e (143-147), and human K,[pGhu-6]. It will be important to indicate the species of origin and the subclass of heavy chain; but it should not be necessary to specify the domain, provided that the complete numbered sequence of the chain in question has been reported in the literature (to which reference would presumably be made in any publica- tion in which the peptide is referred to). If this is not the case, it will be necessary to specify the full primary sequence of the synthesized peptide, prefer- ably using the three letter code (unless lack of space dictates otherwise). Indeed, at an appropriate posi- tion in any publication (e.g., as a table or footnote), it would be expected to provide the full peptide sequen- ces alongside the nomenclatures which have been assigned to them. It is customary now to specify the numbers of the amino acids comprising the synthesized sequence on the line and in parentheses; rather than below, as a subscript (as was the practice in referring to peptide hormones, etc. in the past). Analogues It is important to specify when synthetic peptides are derivatives of sequences contained within the native immunoglobulin polypeptide chain structure. Thus the use of [ ] indicates that the peptide referred to is an analogue; and the substitutions or modifications in the analogue are indicated as to type (the amino acid identified by three-letter code). The use of ( ) within the square brackets specifies further substitution; whilst superscripted number(s) indicate the residue at which the substitution, removal or addition occurs. Obviously, where there have been several substitu- tions (or derivatizations) of particular residues in the parent peptide it will not be feasible to give anything but the full modified sequence. But, where such changes have been minimal, an abbreviated nomen- clature would be useful. Examples of these are: human yV (289-298) [D-Thr98] human Yi (289-298) [Asn29] human y1 (289-298) [Gly (NH2)298] human y, (289-298) [Glu93, Lys297] human yi (289-298) [Asn(CHO)-7]. As indicated in the third example above, and in one of the examples given in the previous section, it is necessary to indicate whether the COOH-terminal carboxyl or the NH2-terminal a-amino group has been derivatized. Allotypic differences can be identified in the same manner as substitutions, provided that the reference sequence is understood or there is agreement as to the original form. For example: human Y3 (289-298) [Thr2"]-referring to the G3m(g) allotype human y3 (289-298) [Phe296]-referring to the nG3m(g) allotype. Proteolytlc and chemical cleavage fragments It is assumed that the currently accepted nomen- clature referring to cleavage fragments of immuno- globulins (for example, Fc, Fab, Fc', F(ab')2, Facb, pFc', tFc', TLmFc, etc.) will continue to be used, in which case it is suggested that such products are referred to as fragments rather than as peptides, as has sometimes been the practice (e.g., Morgan et al. (11)). References 1. Boackle, R.J. et al. An IgG primary sequence theory for complement activation using synthetic peptides. Nature, 282: 742-743 (1980). 2. Burt, D.S. et al. Analysis of the interaction between rat immunoglobulin E and rat mast cells using anti- peptide antibodies. Molecular immunology, 24: 379- 389 (1987). 3. Clccimara, F. et al. Localisation of the IgG effector site for monocyte receptors. Proceedings of the National Academy of Sciences of the USA, 72: 2081- 2083 (1975). 110 WHO Bulletin OMS. Vol 68 1990. Nomenclature for synthetic peptides representative of Immunoglobulin chain sequences 4. Duncan, A.R. & Winter, G. The binding site for Clq on IgG. Nature, 332: 738-740 (1988). 5. Gergely, J. et al. Binding characteristics and isotype specificity of Fc receptors in K cells. Molecular immunology. 23: 1203-1209 (1986). 6. Gherman, M. et al. Regulation of human natural cytotoxicity by IgG. 1. Characterisation of the struc- tural site on monomeric IgG responsible for inhibit- ing natural killer cell activity. Molecular immunology, 24: 743-750 (1987). 7. Hamburger, R.N. Peptide inhibition of Prausnitz- Kustner reaction. Science, 189: 389-390 (1975). 8. Helm, B. et al. The mast cell binding site on human immunoglobulin E. Nature, 331: 180-183 (1988). 9. Hobbs, M.V. et al. Fc peptide mediated regulation of the immune response. II. Analysis of secreted immunoglobulin classes, accessory cell contribution and lymphocyte proliferation in p23 stimulated spleen cell cultures. Journal of immunology, 134: 2847-2852 (1985). 10. Lukas, T.J. et al. Inhibition of Cl-mediated immune haemolysis by monomeric and dimeric peptides from the second constant domain of human immuno- globulin G. Journal of immunology, 127: 2555-2560 (1981). 11. Morgan, E.L. et al. Isolation and identification of a biologically active peptide derived from the CH3 domain of human IgGl. Proceedings of the National Academy of Sciences of the USA, 79: 5388-5391 (1982). 12. Morgan, E.L. et al. Synthetic Fc peptide mediated regulation of the immune response. 1. Characterisa- tion of the immunomodulatory properties of a synth- etic 23 amino acid peptide derived from the sequence of the CH3 domain of IgGl. Journal of experimental medicine 157: 944-947 (1983). 13. Najjar, V.A. & Nlshloka, K. Tuftsin-a physiological phagocytosis-stimulating peptide. Nature, 228: 672- 673 (1970). 14. Ratcliffe, A. & Stanworth, D.R. The use of synthetic y- chain peptides in the localisation of the binding site(s) on human IgGl for the Fc receptors of homo- logous monocytes and heterologous mouse macro- phages. Immunology letters, 4: 215-221 (1982). 15. Sarmay, G. et al. The effect of synthetic peptides corresponding to Fc sequences in human IgGl on various steps on the B cell activation pathway. European journal of immunology, 18: 289-294 (1988). 16. Stanworth, D.R. Application of synthetic peptides representative of immunoglobulin sequences to the delineation of receptor binding and signalling processes. Molecular immunology, 19: 1245-1254 (1982). 17. Stanworth, D.R. et al. The use of synthetic peptides in the delineation of immunoglobulin antigenic epitopes and Fc effector functions. Ciba Foundation Sym- posium 119, 1986, pp. 226-244. WHO Bulletin OMS. Vol 68 1990. 111