A novel family of leucocyte surface antigens

may represent a specific class of evolutionarily-conserved receptorassociated ion channels.

Several recently cloned cDNAs have been found to encode membrane (glyco)proteins of characteristic structure: a 200-300 amino acid polypeptide that probably crosses the membrane four times. Among these molecules are the human leucocyte antigens CD9 (Ref. 1), CD37 (Ref. 2), CD53 (Ref. 3), CD63 (identical to the previously described melanoma-associated antigen ME491) 4, TAPA-1 (Ref. 5) and R2 (Ref. 6), as well as rat CD37, OX-44 (CD53 homologue) and Schistosoma mansoni antigen Sm23 (Ref. 7). Expression of some of these antigens is restricted. For example CD9 is found on thrombocytes and pre-B cells; CD37 is found mostly on B cells; CD53 is a pan-leucocyte molecule; and R2 appears to be an early activation marker. Other antigens such as TAPA-1 are broadly expressed, whereas CD63 is a ubiquitous component of lysosomal membrane and is also present on the surface of some cells. Although the biological function of these molecules is unknown, there are several clues. First, the structure is reminiscent of ion channels or other transport molecules. Second, noncovalent association with other membrane components has been observed in several cases: TAPA-1 with the Leu-13 antigen, CD9 with the thrombocyte integrin gplIb/IIIa and, most interestingly, the rat homologue of ME491 (CD63) with FceRI (Ref. 8). Furthermore, monoclonal antibodies (mAbs) against some of these membrane molecules elicit functional responses when added to some cell types that express them. For example, an anti-CD53 mAb stimulated oxidative burst in monocytes (authors' unpublished observations); anti-CD9 mAbs induce homotypic adhesion of pre-B-cell lines and activation of thrombocytes; an anti-TAPA-1 mAb inhibits cell proliferation and antibodies against the CD63 (ME491) antigen may block IgE-mediated histamine release, modify adhesive properties of some cells and even inhibit transcription of ribosomal RNA genes 9. It is possible that the members of this new, structurally distinct, family

Vficlav Ho~ej~i Institute of Molecular Genetics, Czechoslovak Academy of Sciences, 142 20 Praha 4, Czechoslovakia.

References 1 Boucheix, C., Benoit, P., Frachet, P. et al. (1991)J. Biol. Chem. 266, 117-122 2 Classon, B.J., Williams, A.F., Willis, A.C. et al. (1989) J. Exp. Med. 169, 1497-1502 3 Angelisovfi, P., Vl~ek, C., Stefanovfi,

I. et al. (1990) lmmunogenetics 32,

281-285 4 Metzelaar, M.J., Wijngaard, P.L.J., Peters, P.J. et al. (1991) J. Biol. Chem. 266, 3239-3245 50ren, R., Takashi, S., Doss, C. et al. (1990) Mol. Cell. Biol. 10, 4007-4015 6 Gaugitsch, H.W., Hofer, E., Huber, N.E. et al. (1990) J. Immunol. 21, 377-384 7 Wright, M.D., Henkle, K.L. and Mitchell, G.F. (1990) J. Immunol. 144, 3195-3200 8 Kitani, S., Berenstein, E., Merghenhagen, S. et al. (1991) J. Biol. Chem. 266, 1903-1909 9 Rakowicz-Szulczynska, E.M. and Koprowski, H. (1989) Arch. Biochem. Biophys. 271,366-379


IL-1 signal transduction The recent articles by S.B. Mizel (Immunol. Today 1990, 11, 390391) and L.A.J. O'Neill et al. (Immunol. Today 1990, 11, 392-

394) on interleukin 1 (IL-1) and signal transduction pathways were very interesting. There is clearly still some confusion about the matter but it is apparent that more than one second messenger is involved in the process of T-cell activation by IL-I. We I have recently shown that IL-1 activates two signal transmission pathways in the TH2-cell line D10A: there is both an increase in the accumulation of cyclic AMP (cAMP) and the translocation of protein kinase C (PKC) from the cytosol to the membrane, which are activated by different IL-1 receptors (IL-1Rs) 2. Whereas the increase in cAMP is mediated by the 80 kDa IL-1R 3, the activation of PKC is linked to an independent receptor, cAMP is not the only pathway activated by the IL-1-80 kDa IL-1R interaction since a tyrosine kinase(s) is also activated by this receptor (E. Mufioz, A. Zubiaga, C-K. Huang and B.T. Huber, unpublished). A second IL-1R has recently been cloned; this gene codes for a 68 kDa protein that is expressed in B cells and in TH2 cells4, confirming the data of R. Solari s that suggested that TH2 cells express 80kDa and 68 kDa IL-1Rs.

Immunology Today


It is likely that these two receptors activate different signal transduction pathways, as we have shown in the D10A cell line. The expression of two different IL-1Rs linked to different second messengers may be very important in the process of thymic maturation. There is some evidence that both receptors are expressed in the thymus: approximately 10% of unseparated thymocytes express a large number of 80kDa IL-1Rs corresponding mainly to immature thymocytes (Ref. 2 and A. Zubiaga, pers. commun.). The addition of IL-1 induces the accumulation of diacylglycerol 6 and the activation of the PKC pathway 7 in thymocytes, probably independently of the 80 kDa IL-1R (Ref. 2). Agents that elevate cAMP induce apoptosis in isolated thymocytesS; so it is possible that immature thymocytes accumulate more cAMP in response to IL-1 through the 80 kDa IL-1R than mature thymocytes do and that they then undergo apoptosis. In contrast, in mature thymocytes the activation of PKC by IL-1 could inhibit T-cellreceptor-mediated apoptosis 7. The balance in the expression of two independent IL-1Rs in different subpopulations of thymocytes may, therefore, play an important role in the tightly regulated process of T-cell maturation at two levels: in immature T cells IL-1 may enhance programmed cell death, whereas in

rot 12 No. 8 1991

more mature thymocytes it may prevent this apoptosis. These effects would be mediated by different IL-1Rs. Eduardo Mufioz Blanco

Departamento de Bioquimica y Biologfa Molecular, Facultad de Medicina, Avenida Menendez Pidal s/n, C6rdoba 14004, Spain.

The NeuroendocrineImmune Network edited by Serem Freier, CRC Press, 1990. £120.00 (ix + 266 pages) ISBN 0 8493 4625 8 In the preface of this brief volume, the editor reminds the reader that the various organ systems that make up the human body do not function in isolation, but that "... all the so-called systems" interact with each other. The purpose of The Neuroendocrine-Immune Network is to provide the reader with specific examples of integration of organ systems and it is, therefore, a good introduction to the new and emerging field of neuroendocrinimmunology. It does not begin with a general overview of this broad field, but contains chapters that describe specific examples of neuroimmune interactions. Each chapter contains a table of contents that provides a helpful outline of the material covered. Most chapters introduce the reader to an aspect of the neuroendocrineimmune network with a general introduction to the specific organs and cell types involved. The evidence for the innervation of mast cells is given only after the reader has a knowledge of the major classes of rat mast cell as defined by location and responses to neurotransmitters and growth factors. Similarly, a brief introduction to the immunobiology of the thymus prepares one to place into context the role of the neural crest in the development of the thymus. Tables and figures are plentiful as well as full-page photomicrographs and color plates. All of the chapters

References 1 Mufioz, E., Beutner, U., Zubiaga, A. and Huber, B.T. (1990),1. Immunol. 144, 964-969 2 Mufioz, E., Zubiaga, A., Sims, J.E. and Huber, B.T. (1991)J. Immunol. 146, 136-143 3 Sims, J.E., March, C.J., Cosman, D. et al. (1988) Science 241,585-589 4 Durum, S.K., Quinn, D.G. and Muegge, K. (1991) lmmunol. Today

12, 54-57 5 Solari, R. (1990) Cytokine 2, 21-28 6 Rosoff, P.M., Savage, N. and Dinarello, C.A. (1988) Cell 54, 73-81 7 McConkey, D.J., Hartzell, J.P., Chow, S.C., Orrenius, S. and Jondal, M. (1990)J. Biol. Chem. 265, 3009-3011 8 McConkey, D.J., Orrenius, S. and Jondal, M. (1990) J. Immunol. 145, 1227-1230

are of a reasonable length (10-15 pages) except for a chapter concerning the hormonal influence on the secretory immune system of the eye. This particular chapter contains 12 figures from previously submitted or published works by the author; perhaps, as with most multi-authored texts, this one may have profited from more assertive editing. Each of the 16 chapters is written by someone active in the field and the most recent references cited are from 1989. At its core, this volume contains much evidence for regulatory neural pathways of primary and secondary lymphatic tissue. However, other topics dealt with in this book are the immunoregulatory properties of pituitary hormones, opioids, sex steroids, substance P, neurotensin and vasoactive intestinal peptide. Thus, this book strikes a good balance between the neural and endocrine pathways of immune system regulation. One chapter dealing with the possible immunomodu-

latory effects of leukotriene B4 and platelet-activating factor (PAF) may appear to be out of step with the overall theme of the book, except when one considers the nervous system production of these proinflammatory mediators. Perhaps the best chapter is the last one of the volume, written by the editor, in which he discusses the immune, endocrine and nervous system interactions in the digestive tract with a particular emphasis on the regulation of immunoglobulin secretion by cholecystokinin. This readable volume is apparently aimed at the basic science oriented researcher and provides a breadth of information. It is a good introductory text to a complex and rapidly growing field. I do recommend it.

Bryan L. Spangelo Dept of Physiology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA.


Therapeutic Monoclonal Antibodies edited by Carl A.K. Borrehaeck and James W. Larrick, Stockton Press, 1990. £55.00 (xiii + 369pages) ISBN 0 333 $3S44 8 Antibody therapy of human disease has a history extending over almost a century since the first trial of antiserum to diphtheria toxin. However,

Immunology Today


polyclonal antibodies are not ideal therapeutic agents, because they are derived from live animals and are heterogeneous. The development of the technology for producing monoclonal antibodies (mAbs) and for manipulating antibody genes has revolutionized antibody therapy. Therapeutic Monoclonal Antibodies reflects many of the advances and the attendant problems of recent years. A major theme is the potential advantage of human mAbs. The use

Vol 12 No. 8 1991

IL-1 signal transduction.

A novel family of leucocyte surface antigens may represent a specific class of evolutionarily-conserved receptorassociated ion channels. Several rec...
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