leidoscope HIV and idiotypic T-cell regulation: another view There has been a recent surge of interest in promoting the link between human immunodeficiency virus (HIV) and the network view of the immune system. A concise review of the relevant data was presented by Michael Grant (Immunol. Today, 1991, 12, 171-172). According to our results, an additional route of HIV gp120 interaction with the immune system may exist. The regulation of the immune response depends partly on interactions between immunoglobulin (Ig) family members by recognition of their idiotypes (Id). This network theory of immune relations proposed by Jerne I in terms of antibodies and B-cell interaction now encompasses T cells which also express idiotypes on their antigen receptors. The programmed appearance of Id elements seems to be developmentally controlled and a key role in this process is played by early expressed variable heavy (VH) chains of group III genes-'. Any event that upsets this balance may cause autoimmunity. Recently, in the context of an idiotypic network that links HIV gpl20, major histocompatibility complex (MHC) class II molecules and the T-cell receptor (TCR), models for HIV-induced
Immunology: Recognition and Response edited by William E. Paul, W.H. FreemanandCo., 1991. £10.95 (viii + 168 pages) ISBN 0 7•67 2223 2 Immunology: Recognition and Response reprints a collection of articles, originally published in Scientific American between 1980 and 1990. The eclectic choice of subjects is roughly grouped into five sections that contain one, two or three chapters. Each is a self-contained treatise, although the sections are preceded by an introduction in
pathogenesis have been suggested ~,4. Our recent results show homology between lg heavy chain variable region (a product of group I11 genes) and gp120 (Refs 5-7). The region of homology involves a reported T-cell epitope (T) and one of the B-cell epitopes (B2) of gpl20, and the amino-terminal portion of the Ig V H chain of corresponding length, that includes FW1, CDR1 and part of FW2. (This may also be defined as the portion comprising the third hypervariable region, or V3 loop, and ten residues upstream.) The fact that the Ig shares an invariant amino acid sequence with the gpl20 hypervariable region suggests that gpl20 may possess some of the individual structural Ig elements or Id. If so, we propose that gp120 may take part in the activation of Id-specific T-cell populations subserving helper, suppressor or even cytotoxic activities. The generation of Id-specific T cells occurs via direct interaction with the ld structures on lgs or with the processed form of Id of Iff. Thus, sequential development of the immune response may be altered by the appearance of gpl20-bearing Id structures with complementarity to T-cell idiotypes. Furthermore, the existence of the recombination elements in gpl20 gives rise to the possibility that HIV infection may disturb developmentally-regulated
References 1 Jerne, N.K. (1974) Ann. lmmunol. 142,373-389 2 Schroeder, H.W., Jr and Wang, J.Y. (1990) Proc. Natl Acad. Sci. USA 87, 6146-6150 3 Habeshaw, J.A., Dalgleish, A.G., Bountiff, L. et al. (1990) Immunol. Today 11,418-425 4 Hoffmann, G.W., Kion, T.A. and (;rant, M.D. ( 1991) Proc. Natl Acad. Sci. USA 88, 3060-3064 5 Veljkovid,V. and Metla~, R. (1990) hnmunol. Lett. 26, 193-196 6 Veljkovid,V. and Metla~, R. 1991) hnmunol. Lett. 39, 40-43 7 Metlag, R., Veljkovid, V., Paladini, R.D. and Pongor, S. (1991) Biochem. Biophys. Res. Commun. 179, 1056-1062 8 Pereira, P., Ban&ira, A. and Coutinho, A. (1989) Annu. Rev. Immunol. 7, 209-221 9 Sakato, N., Rugdech, P., Yoda, T. et al. (1990) Immunology 71, 153-157
which the editor attempts to draw out a common theme. Some chapters sit very uneasily together, for example Section III has two cytokine chapters ('Interleukin-2' and 'Tumor necrosis factor') with an article on 'How killer cells kill', under the umbrella 'Regulatory and effector mechanisms of the immune response'. By the end of the book, I was left feeling that the material was given to the editor to sort out, rather than chosen on merit for inclusion. The Scientific American format has a beguiling clarity that offers any newcomer an instant potted history of a subject and a code-breaker for the inevitable jargon. The trade-off
for this positive aspect is that you often find that you don't get the 'whole truth'. Worse still some authors (even those of international repute) feel bound to inject their writing with tabloid dynamism. The quality of writing varies enormously: Chapter 1, which deserves and is given a section of its own, is a handsomely described history of clonal selection. Gordon Ada and Gustav Nossal write with the authority and insight of individuals close to the promulgators of the clonal selection theory. In contrast, try this, for example, from John Ding-E Young and Zanvil Cohn on 'How killer cells kill' "Their primary duty
Immunology Today
38
VH-chain expression 6,7. If this predicted Id-specific T-cell activation by HIV-1 gpl20 V3 loop occurs, then usage of this neutralization epitope as a component of an anti-AIDS vaccine should be reexamined.
V. Veljkovii R. Metla~ Laboratory for Multidisciplinary Research, Boris Kidrich Institute, PO Box 522, 11001 Beograd, Yugoslavia.
Vol. 13 No. 1 1992
Immunology: Recognition and Response edited by William E. Paul, W.H. FreemanandCo., 1991. £10.95 (viii + 168 pages) ISBN 0 7•67 2223 2 Immunology: Recognition and Response reprints a collection of articles, originally published in Scientific American between 1980 and 1990. The eclectic choice of subjects is roughly grouped into five sections that contain one, two or three chapters. Each is a self-contained treatise, although the sections are preceded by an introduction in
pathogenesis have been suggested ~,4. Our recent results show homology between lg heavy chain variable region (a product of group I11 genes) and gp120 (Refs 5-7). The region of homology involves a reported T-cell epitope (T) and one of the B-cell epitopes (B2) of gpl20, and the amino-terminal portion of the Ig V H chain of corresponding length, that includes FW1, CDR1 and part of FW2. (This may also be defined as the portion comprising the third hypervariable region, or V3 loop, and ten residues upstream.) The fact that the Ig shares an invariant amino acid sequence with the gpl20 hypervariable region suggests that gpl20 may possess some of the individual structural Ig elements or Id. If so, we propose that gp120 may take part in the activation of Id-specific T-cell populations subserving helper, suppressor or even cytotoxic activities. The generation of Id-specific T cells occurs via direct interaction with the ld structures on lgs or with the processed form of Id of Iff. Thus, sequential development of the immune response may be altered by the appearance of gpl20-bearing Id structures with complementarity to T-cell idiotypes. Furthermore, the existence of the recombination elements in gpl20 gives rise to the possibility that HIV infection may disturb developmentally-regulated
References 1 Jerne, N.K. (1974) Ann. lmmunol. 142,373-389 2 Schroeder, H.W., Jr and Wang, J.Y. (1990) Proc. Natl Acad. Sci. USA 87, 6146-6150 3 Habeshaw, J.A., Dalgleish, A.G., Bountiff, L. et al. (1990) Immunol. Today 11,418-425 4 Hoffmann, G.W., Kion, T.A. and (;rant, M.D. ( 1991) Proc. Natl Acad. Sci. USA 88, 3060-3064 5 Veljkovid,V. and Metla~, R. (1990) hnmunol. Lett. 26, 193-196 6 Veljkovid,V. and Metla~, R. 1991) hnmunol. Lett. 39, 40-43 7 Metlag, R., Veljkovid, V., Paladini, R.D. and Pongor, S. (1991) Biochem. Biophys. Res. Commun. 179, 1056-1062 8 Pereira, P., Ban&ira, A. and Coutinho, A. (1989) Annu. Rev. Immunol. 7, 209-221 9 Sakato, N., Rugdech, P., Yoda, T. et al. (1990) Immunology 71, 153-157
which the editor attempts to draw out a common theme. Some chapters sit very uneasily together, for example Section III has two cytokine chapters ('Interleukin-2' and 'Tumor necrosis factor') with an article on 'How killer cells kill', under the umbrella 'Regulatory and effector mechanisms of the immune response'. By the end of the book, I was left feeling that the material was given to the editor to sort out, rather than chosen on merit for inclusion. The Scientific American format has a beguiling clarity that offers any newcomer an instant potted history of a subject and a code-breaker for the inevitable jargon. The trade-off
for this positive aspect is that you often find that you don't get the 'whole truth'. Worse still some authors (even those of international repute) feel bound to inject their writing with tabloid dynamism. The quality of writing varies enormously: Chapter 1, which deserves and is given a section of its own, is a handsomely described history of clonal selection. Gordon Ada and Gustav Nossal write with the authority and insight of individuals close to the promulgators of the clonal selection theory. In contrast, try this, for example, from John Ding-E Young and Zanvil Cohn on 'How killer cells kill' "Their primary duty
Immunology Today
38
VH-chain expression 6,7. If this predicted Id-specific T-cell activation by HIV-1 gpl20 V3 loop occurs, then usage of this neutralization epitope as a component of an anti-AIDS vaccine should be reexamined.
V. Veljkovii R. Metla~ Laboratory for Multidisciplinary Research, Boris Kidrich Institute, PO Box 522, 11001 Beograd, Yugoslavia.
Vol. 13 No. 1 1992
