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Cell surface receptors in development and immunity: A speculative review
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY, Vol. iO, pp. 279-284, 1986. O145-305X/86 $ 3.00 + .00 Printed in the USA. Copyright (c) 1986 Pergamon Journals Ltd. All rights reserved.
CE~L SURFACE RECEPTORS IN DEVeLOPmeNT ~.ND IFS.~JNITY: A SPECULATIVE R~L-V]!Z4
Scott F. Gilbert Department of Biology Swarthmore College Swarthmore, PA 19081
The past two years has seen dramatic changes in our conception of cell surface receptors and intercellular communication. On one hand, new cell surface molecules are being discovered weekly, such that one hesitates to pick up one's Journals for fear of having to find time to learn of still yet another set of new cell surface molecules. A quick literature search shows that whereas total articles referenced in BioAbstracts has increased 1.4-fold since 1970, the nu]nber of articles listing receptors in their titles or abstracts has Increased 13-fold. On the other hand, this tendency towards mu/tiplicity has been balanced by discoveries suggesting that the multifarious lig~_nd-receptor ~ s t e m s described may operate by common rules, and indeed, through common molecules. The past two years have seen the translocation of the elusive T-cell antigen receptor from a useful hypothesis to a set of 2 polypeptides having amino acid sequences derived from eight genetically separate regions (I-2). The T4 antigen of human helper T-lymphocytes was shown not only to be neces~ary for antigen recognition in self-context (3,4) but was also demonstrated to be the receptor for LAV/HTLV-III, the viral cause of the acquired immune deficiency syndrome, AIDS (5,6). Since the T4 molecule is important in inducing the transformation from B-lymphocyte to plasma cell, it is an important cell surface signalling molecule in both developmental and i~_~unologlcal studies. The use of B-cell induction by T-cells, macrophages, and antigen to model developmental inductions in embryos has become more important as similarities have been found between the developing cells of the embryo and the developing immune cells of the adult. The crossllnking of Bcell antigen receptors has been found to produce changes in the actin cytoskeleton (7,8), changes in second messengers (9) and the formation of a new set of growth factor receptors (10). These four phenomena, the crossllnking of cell surface receptors, changes in cytoskeletal architecture, secondary message production, and the expression of new growth 279
280
CELL SURFACE RECEPTORS
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I0, No. 2
receptors upon induction are also being seen in e:bryological interactions (for instance 11, 12-13). The ~nduction of the transferrin receptor after cell contact in kidney morphogenesis (14) is especially interesting in this conte~-t, since changes in extracellular matrix binding and intermediate filament cyto~:eleton organization are also observed (15,16). During the past two years, the use of monoclonal antibodies has identified more and more cell surface proteins and has correlated them with intercellular events such as compaction, trophoblast attachment, primary endoderm formation (17), lymphocyte differentiation (18), lineage separation (19), and positional information (20). In r any cases we now have identified antigens for which we can associate no known function. This situation should yield new information concerning functions of which we are not yet aware. The year's headlines on cell surface receptors were capped, of course, by the awarding of the ~obel Prize for Physiology and F edicine to ~.tichael Brown and Joseph Goldstein for their characterization of the receptor for low density lipoprotein. Thus, the ~fristotelians who delight in diversity and in structure/function correlations have ~ o w n great joy these two years. Moreover, so have the Platoni~ts who glory in seeing the common unity underlying the apparently disparate phenomena. One facet of cell surface receptor research that has united immunology and develop~.~ent is the notion of a triggering reaction. During the past two years, it has been shown that the binding of an agent to its receptor in several different cellular systems leads to the ~roduction of two new molecules. These newly discovered second messengers are diacylglycerol and inositol triphospate. The receptors can be as diverse as the acetylchollne receptor of ~ o o t h muscle or brain cells, the antigen receptors of B-lymphocytes or leukemic basophils, the photon receptors of retinal neurons, or the sp.er~ receptors of sea urchin eggs (reviewed in 21). In each case, the reception of the signal on the cell surface is transduced into the cell by the er~ymatlc synthesis of those two messengers. To make the story more complete, it appears that oncogenes act at any of three stages of growth regulation. Their products may mimic growth factors, occupied growth factor receptors, or some molecule on the intracellular pathway Icadirg to cell division. The v-s~_s oncogene carried by the simian sarcoma virus and the v-fins o~cogene of the feline sarco-a virus produce proteins re~e:bling platelet-derived growth factor and granulocyte-macrophage colony-stimulating factor, respectively (22-24). ~3~en tLe~e viruses infect cells bearing the receptors for these factors, the cells divide in what appears to be the result of autocrine" stimulation. The avian erythroblastosis virus carries an oncogene v-_erbB which seems to resemble the epithelial growth factor receptor ~n its activated form (25). Berrldge and Irvine (21) have speculated that diacylglycerol and inosine triphosphate might be involved in relaying the growth signal from the membrane to the nucleus. Diacylglyeerol stimulates the C-kinase (the site of phorbol ester tumor promotion) to activate the Na+/H + exchange which elevates intracellular pH, and inosltol phosphate releases Ca ++ from the e n d o p l a ~ i c reticulum. The free calcium ~ons and high pH are thought to prepare cells for DNA synthesis. Thus, the cell surface receptor-dependent activation of egg development, lymphocyte differentiation, cell growth, and hormone regulation may all be related to a common mechanl sin. Other common features of intercellular communication are appearing in studies of sperm-egg attachment. For developmental biologists, this is the archetypal cell-cell interaction, and it may be the interaction that links protists to multlcellular organisms. The pattern that emerges from studies of sperm/vitelline envelope binding in sea urchins (26) sperm/zona binding in mice (27,28) and sperm/chorion binding in ascidlans (29) is that a sperm cell surface protein recognizes carbohydrate groups on the egg surface. Furthermore, glycoslytransferases are found on the isogametic cell surfaces of
Vol. IO, No. 2
CELL SURFACE RECEPTORS
281
_C_h_l_e~_dom_o_nas as well (rc%.iewed in 30). It a[Fears that protein-carbohydrate interaction may be a general mechanism in binding gametes together. What's good for gametes might well have been modified for the e~bryonic cell interactions. Cell surface g/ycosyltransferases have been implicated in the migration of gastrulating cells, in the inductive interface of optic cup/ectoderm, medullary plate/prescmitic mescderz, and notochord/sc-ite (31), and in the condensation of c.hondrocytes during i~mb d e v e ! o ~ e n t (reviewed in 30). Furukawa and coworkers (32) have ~hown that class II ]<~C g!ycoproteins have g!ycosyltransferase activity, and antibodies to a [urified g!ycosyltransferase cross-reacts with im~,unoglobulins (33). The carbo,~Jydrate chains of glycoproteins are essential for cezFaction and for the adhesive properties of the neural cell adhesion mc!ecule .'~-CAF. (34,35). It is possible, then, that the protein-carbohydrate bonding utilized in protist cor~jugation t ecame specialized for sperm-egg binding, later specialized for c.--_bryonic cell-cell interactions, and then later still modified for cell-cell interactions in the immune sD'stem. Another feature of cell-cell interactions coming cut of fertilization research is the need to cluster one's receptors. Eossignol and ccworkers (26) have speculated that whereas ~ a l l ligands such as hormones can bind to and effect charges in solitary receptors, you may need a cluster of them to hold a wiggling sperm. Toposomes or adherons have been isolated in several ~ b r y o n i c o r g a n i c s and may have two functions (20,36). The first is to hold the cells together while the second is to provide positional information by altering the geometry of those receptors. Clustering of receptors may also be needed to effect the immune response of B-cells (37) and to fasciculate neurons together
(35). The integration of irnunology and develo.~ent was clearly seen by F.R. Li/lie (38) who studied sperm-egg binding using ir_~,unolcgical techniques and discussed it in immunological language. He had to apologize to his readers for this new tongue: "The terminology has been largely adopted from immunology, because it s e ~ e d best suited to express the facts, if it seems rather bizarre to the zoological reader, I must ask him not to conceive prejudice for this reason against the facts thc~selves... " Lillie's paper is fascinating to read for its s;ecr/ation concerning bow the reception of sperm by the egg created changes within the egg. He postulated a molecule, fertil~zin, which had a s~erm binding site exposed outside the cell and which had another site inside the cell. This latter site was not active until the outer site bound the s~
I would like to thank Dr. David Sonneborn for pointing out the transduction aspect of Lillie's fertillzin model.
P,EFE REN CES I.
Sire, G., Yague, J., Nelson, J., Marrack, P., Palmer, E., Augustin, A., and Kappler, J. Primary structure of human T-cell receptor alpha chain. ~'ature 312, 771, 1984.
282
2.
CELL SURFACE RECEPTORS
Vol. IO, No. 2
Born, W., Yag~]e, J., Palmer, E., Kappler, J., and Marrack, P. Rearrangement of T-cell receptor beta-chain genes during T-cell development. Pro_cL_N_at~__A_ca_d.__S_c]~U_S_A82, 2925, 1985.
.
Ymrrack, P., Endres, R. Shimonkevitz, R., Zlotnik, A., Dialynas, D., Fitch, F., and Kappler, J. The major histocompatibility complexrestricted antigen receptor on T-cells. II. Role of the L3T4 product. J, Exp._ Med. 158, I077, 1983.
.
Swain, S.L., Dialynas, D.P., Fitch, F.W., and English, M. ~onoclor~l antibody to L3T4 blocks the function of T-cells specific for class 2 Eajor histocompatibility complex antigens. J~_Y~_~®_un_o~_._13_2,1118, 1984.
.
De~eish, A.G., Beverley, P.C.L., Clapham, P.R., Crawfcrd, D.H., Greaves, M.F., and Weiss, R.A. The CD4 (T4) antigen is an essential com;~nent of the receptor for the AIDS retrovirus, l~ature 312, 763, 1984.
.
Klatzmann, D., Champagne, E., Chamaret, S., Gruest, J., Guetard, D., Thierry, H., Gluckman, J.C., and Montagnier, L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 31_2, 767, 1984.
.
Fl~na~an, J. and Koch, T. Nature 273, 278, 1978.
.
Woda, B.A. and Woodin, M.B. The interaction of lymphocyte m ~ b r a n e proteins with the lymphocyte cytcskeletal matrix. _J~__I=T~9_u_n_ol_~_133,2767, 1984.
.
Coggeshall, K.M. and Cambier, J.C. B-cell activation VIII. N~mbrane immunoglobulins transduce signals via activation of phosphatidylinositol hydrolysis. J. I~__muD_o_lj_1_33,3382, 1984.
Cross-linked surface Ig attaches to actin.
10.
Yaffe, L.J. and Finkelman, F.D. Induction of B-lymphocyte receptor for T-cell replacing factor by crosslinking of surface IgD. _P_r99_.__N_a_t~_Ac~_d~ Sol USA 80, 293, 1983.
11.
Hadley, M.A., Byers, S.W., Suarez-Quian, C.A., Kleinman, H.K., and Dym, M. Extracellular matrix regulates Sertoli cell differentiation, testicular cord formation, and germ cell development in vltrQ. J,__Cg_l]~ Bio~_. 101, 1511, 1985.
12.
Solursh, M., Jensen, K.L., Zanetti, N.C., Linsenmeyer, T.F., and Reiter, R.S. Extracellular matrix mediates epithelial effects on chondrogenesis in v~tro. Devel~ Bilo_~j_jO~, 451, 1984.
13.
Sugrue, S.P. and Hay, E.D. Interaction of embryonic corneal epithelium with exogenous collagen, lamlnin, and fibronectin: Role of endogenous protein synthesis. Dey_el. B_iol~_~2, 97, 1982.
14.
Ekblom, P., Thesleff, I., SaxOn, L., Miettinen, A., and Timpl, R. Transferrin as a fetal growth factor: Acquisition of responsiveness related to embryonic induction. _~9~__N_a_tj__A_c~_d~__S_c_i~__U_SA__8_0, 2651, 1 983.
15.
Lehtonen, E., Virtanen, I., and SaxOn, L. Reorganization of intermediate filament cytoakeleton in induced metanephric mesenchyme cells is independent of tubule morphogenesis. Devel. Biol. I08, 481, 1985.
Vol. I0, No. 2
CELL SURFACE RECEPTORS
16.
Vcstwebcr, D., Kemler, R., and Ekblom, P. Cell-acLbesion molecule uvomorulin during kidney development. De~l_el_~_Bio]= 112, 213, 1985.
17.
Richa, J. Damsky, C.H., Buck, C., Knowles, B.B., and Solter, D. Cell surface glycoproteins mediate comFaction, trophoblast attachment, and endoderm formation during early mouse development. De~9~__B]91,._J08 , 513, 1985.
18.
Rothenberg, E. and Lugo, J.P. Differentiation and Cell Division in the !t%5:malian Thymus. D~_el__._Big]_._]12, I, 1985.
19.
$esse, J., Horwitz, A., Pacifici, M., and Ho!tzer, H. Separation of precursor mycgenic and chondrogenic cells in early limb bud ,-esenchyme by a monoclonal antibody. J. Ce_l_l__B_~_ol~_9_9,1856, 1984.
20.
No!!, H., ~latranga, V., Cervello, M., Hu~phreys, T., Ku-~'asaki, B., and A~elson, D. Characterization of toposomes from sea urchin blastula cells: A cell organe!le mediating cell adhesion and expressing positional information, Pro_c~__N_a_t~_A_cg__d~_Sc$_USA,82, 8062, 1985.
21.
Berridge, M.J. and Irvine, R.F. Inositol triphosphate, a novel second zessenger in cellular signal transduction. Nature332, 315, 1984.
22.
Lang, R.A., Metcalf, D., Gough, N.M., Dunn, A., and Gonda, T.J. Expression of a hemopoietic growth factor cDNA in a factor-dependent cell line results in autonomous growth and tumorigenicity. Cell ~3, 531, 1985.
23.
Vaterfield, M.D., Scrace, G.T., ~q~ittle, N., Stoobant, P., Johnsson, A., k'asteson, A., Westermark, B., Heldin, C-H, Huang, J.S. and Deuel, T.F. P!atelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature 3_04, 35, 1983.
24.
Cniu, I-M, Reddy, E.P. Givol, D., Robbins, D.C., Tronick, S.R., and iaronson, S.A. !,'ucleotide sequence analysis identifies the hu~an c-sls proto-cncogene as the structural gene for platelet-derived growth factor Cell 3[, 123, 19~4.
25.
Dow.~'ard, J., Yarden, Y., Mayes, E., Scrace, G., Totty, N., Stockwell, P., U!lrlch, A., Schlesslnger, J., and Waterfield, M.D. Close similarity of epidermal growth factor and the v-erbB oncogene protein sequences. ?:ature 3_01, 521, 1984.
26.
Rossignol, D.P., Earles, B.~J., Decker, G.L., and Lennarz, W.J. Characterization of the sperm receptor on the surface of eggs of S ti_o.D~y]p_c_e_n_t_r_o_t_u_s__P_UrCDuratg_s, D_e]{_e~__B_i_o]~_]_O_4, 308, 1984.
27.
Lopez, L.C., Bayna, E.M., Litoff, D., Shaper, N.L., Shaper, J.H., and Shur, B.D. Receptor function of mouse sperm surface galactosyltransferase during fertilization. J, C_e~]_B~tgl~ 101, 1501, 1985.
28.
Florman, H.M. and Wassar~an, P.M. O-Linked oligosaccharides of mouse egg ZP3 account for its sperm receptor activity. Cel~__41, 313, 1985.
284
29.
CELL SURFACE RECEPTORS
Vol. iO, No. 2
Desantis, R., Pinto, M.R., Cotelli, F., Rosati, F., Monroy, A., and D'~llesslo, G. A fucosyl glycoprotein component with sperm receptor and srerm activating activities from the v!tellinc coat of Ciona_inle~ina!js eggs. EEx9gr. Ce]l_Rgs~ I~8, 508, 1983.
3O.
Shur, B.D. (1984) The receptor function of galactosyltransferase during cellular interactions. Mol. Cell Biochem 61, 143, 1984.
31.
Shut, B.S. Cell-surface g!ycosyltransferases in gastrulating chick embryos. I. Temporally and spatially specific patterns of four endogenous glycosyltransferase activities. Deye_/~__B_i_oh_5_8,23, 1977.
32.
Furu~'awa, K., Higgins, T., and Roth, S. An affinity purified major histocompatibillty complex (~CqC) antigen with high N-acetylgalactosaminyl transferase activity. J. C_e_l_l_B_ip_l~_j_0j,309a, 1985.
33.
Podolsky, D.K. and Isselbacher, K.J. Characterization of monoclonal antibodies to serum galactosD'Itransferase. Pro_c~_N_a_tj_A__ca_d._S_c_i_US_A_8_!_, 2529. 1984.
34.
Iwakura, Y. and Pmsami, N. Effects of tunicamycin on preimplantation mouse embryos: Prevention of molecular differentiation during blastocyst formation. Deve~..Biol. !1_2, 135, 1985.
35.
Rutishauser, W. Developmental biology of a neural cell adhesion molecule. Nature 3j0, 549, 1984.
36.
Schubert, D. and LaCorblere, M. Isolation of a cell surface receptor for chick neural retina adherons. J. _C_e~l__H_i_o_ij_j_0_0,56, 1985.
37.
Dintzis, R.Z., Vogelstein, B., and Dintzis, H.M. Specific cellular stimulation in the primary immune response: Experimental test of a quantized model. _Proc_.__~.'_a_t~__A_ca_d~__S_cj_. U_S_A__8_0,293, 1983.
38.
Lillie, F.R. Studies on fertilization. VI. The mechanism of fertilization in Arbacla. J~_E_xD~_Z_op~_j6, 523, 1914.
CE~L SURFACE RECEPTORS IN DEVeLOPmeNT ~.ND IFS.~JNITY: A SPECULATIVE R~L-V]!Z4
Scott F. Gilbert Department of Biology Swarthmore College Swarthmore, PA 19081
The past two years has seen dramatic changes in our conception of cell surface receptors and intercellular communication. On one hand, new cell surface molecules are being discovered weekly, such that one hesitates to pick up one's Journals for fear of having to find time to learn of still yet another set of new cell surface molecules. A quick literature search shows that whereas total articles referenced in BioAbstracts has increased 1.4-fold since 1970, the nu]nber of articles listing receptors in their titles or abstracts has Increased 13-fold. On the other hand, this tendency towards mu/tiplicity has been balanced by discoveries suggesting that the multifarious lig~_nd-receptor ~ s t e m s described may operate by common rules, and indeed, through common molecules. The past two years have seen the translocation of the elusive T-cell antigen receptor from a useful hypothesis to a set of 2 polypeptides having amino acid sequences derived from eight genetically separate regions (I-2). The T4 antigen of human helper T-lymphocytes was shown not only to be neces~ary for antigen recognition in self-context (3,4) but was also demonstrated to be the receptor for LAV/HTLV-III, the viral cause of the acquired immune deficiency syndrome, AIDS (5,6). Since the T4 molecule is important in inducing the transformation from B-lymphocyte to plasma cell, it is an important cell surface signalling molecule in both developmental and i~_~unologlcal studies. The use of B-cell induction by T-cells, macrophages, and antigen to model developmental inductions in embryos has become more important as similarities have been found between the developing cells of the embryo and the developing immune cells of the adult. The crossllnking of Bcell antigen receptors has been found to produce changes in the actin cytoskeleton (7,8), changes in second messengers (9) and the formation of a new set of growth factor receptors (10). These four phenomena, the crossllnking of cell surface receptors, changes in cytoskeletal architecture, secondary message production, and the expression of new growth 279
280
CELL SURFACE RECEPTORS
Vol.
I0, No. 2
receptors upon induction are also being seen in e:bryological interactions (for instance 11, 12-13). The ~nduction of the transferrin receptor after cell contact in kidney morphogenesis (14) is especially interesting in this conte~-t, since changes in extracellular matrix binding and intermediate filament cyto~:eleton organization are also observed (15,16). During the past two years, the use of monoclonal antibodies has identified more and more cell surface proteins and has correlated them with intercellular events such as compaction, trophoblast attachment, primary endoderm formation (17), lymphocyte differentiation (18), lineage separation (19), and positional information (20). In r any cases we now have identified antigens for which we can associate no known function. This situation should yield new information concerning functions of which we are not yet aware. The year's headlines on cell surface receptors were capped, of course, by the awarding of the ~obel Prize for Physiology and F edicine to ~.tichael Brown and Joseph Goldstein for their characterization of the receptor for low density lipoprotein. Thus, the ~fristotelians who delight in diversity and in structure/function correlations have ~ o w n great joy these two years. Moreover, so have the Platoni~ts who glory in seeing the common unity underlying the apparently disparate phenomena. One facet of cell surface receptor research that has united immunology and develop~.~ent is the notion of a triggering reaction. During the past two years, it has been shown that the binding of an agent to its receptor in several different cellular systems leads to the ~roduction of two new molecules. These newly discovered second messengers are diacylglycerol and inositol triphospate. The receptors can be as diverse as the acetylchollne receptor of ~ o o t h muscle or brain cells, the antigen receptors of B-lymphocytes or leukemic basophils, the photon receptors of retinal neurons, or the sp.er~ receptors of sea urchin eggs (reviewed in 21). In each case, the reception of the signal on the cell surface is transduced into the cell by the er~ymatlc synthesis of those two messengers. To make the story more complete, it appears that oncogenes act at any of three stages of growth regulation. Their products may mimic growth factors, occupied growth factor receptors, or some molecule on the intracellular pathway Icadirg to cell division. The v-s~_s oncogene carried by the simian sarcoma virus and the v-fins o~cogene of the feline sarco-a virus produce proteins re~e:bling platelet-derived growth factor and granulocyte-macrophage colony-stimulating factor, respectively (22-24). ~3~en tLe~e viruses infect cells bearing the receptors for these factors, the cells divide in what appears to be the result of autocrine" stimulation. The avian erythroblastosis virus carries an oncogene v-_erbB which seems to resemble the epithelial growth factor receptor ~n its activated form (25). Berrldge and Irvine (21) have speculated that diacylglycerol and inosine triphosphate might be involved in relaying the growth signal from the membrane to the nucleus. Diacylglyeerol stimulates the C-kinase (the site of phorbol ester tumor promotion) to activate the Na+/H + exchange which elevates intracellular pH, and inosltol phosphate releases Ca ++ from the e n d o p l a ~ i c reticulum. The free calcium ~ons and high pH are thought to prepare cells for DNA synthesis. Thus, the cell surface receptor-dependent activation of egg development, lymphocyte differentiation, cell growth, and hormone regulation may all be related to a common mechanl sin. Other common features of intercellular communication are appearing in studies of sperm-egg attachment. For developmental biologists, this is the archetypal cell-cell interaction, and it may be the interaction that links protists to multlcellular organisms. The pattern that emerges from studies of sperm/vitelline envelope binding in sea urchins (26) sperm/zona binding in mice (27,28) and sperm/chorion binding in ascidlans (29) is that a sperm cell surface protein recognizes carbohydrate groups on the egg surface. Furthermore, glycoslytransferases are found on the isogametic cell surfaces of
Vol. IO, No. 2
CELL SURFACE RECEPTORS
281
_C_h_l_e~_dom_o_nas as well (rc%.iewed in 30). It a[Fears that protein-carbohydrate interaction may be a general mechanism in binding gametes together. What's good for gametes might well have been modified for the e~bryonic cell interactions. Cell surface g/ycosyltransferases have been implicated in the migration of gastrulating cells, in the inductive interface of optic cup/ectoderm, medullary plate/prescmitic mescderz, and notochord/sc-ite (31), and in the condensation of c.hondrocytes during i~mb d e v e ! o ~ e n t (reviewed in 30). Furukawa and coworkers (32) have ~hown that class II ]<~C g!ycoproteins have g!ycosyltransferase activity, and antibodies to a [urified g!ycosyltransferase cross-reacts with im~,unoglobulins (33). The carbo,~Jydrate chains of glycoproteins are essential for cezFaction and for the adhesive properties of the neural cell adhesion mc!ecule .'~-CAF. (34,35). It is possible, then, that the protein-carbohydrate bonding utilized in protist cor~jugation t ecame specialized for sperm-egg binding, later specialized for c.--_bryonic cell-cell interactions, and then later still modified for cell-cell interactions in the immune sD'stem. Another feature of cell-cell interactions coming cut of fertilization research is the need to cluster one's receptors. Eossignol and ccworkers (26) have speculated that whereas ~ a l l ligands such as hormones can bind to and effect charges in solitary receptors, you may need a cluster of them to hold a wiggling sperm. Toposomes or adherons have been isolated in several ~ b r y o n i c o r g a n i c s and may have two functions (20,36). The first is to hold the cells together while the second is to provide positional information by altering the geometry of those receptors. Clustering of receptors may also be needed to effect the immune response of B-cells (37) and to fasciculate neurons together
(35). The integration of irnunology and develo.~ent was clearly seen by F.R. Li/lie (38) who studied sperm-egg binding using ir_~,unolcgical techniques and discussed it in immunological language. He had to apologize to his readers for this new tongue: "The terminology has been largely adopted from immunology, because it s e ~ e d best suited to express the facts, if it seems rather bizarre to the zoological reader, I must ask him not to conceive prejudice for this reason against the facts thc~selves... " Lillie's paper is fascinating to read for its s;ecr/ation concerning bow the reception of sperm by the egg created changes within the egg. He postulated a molecule, fertil~zin, which had a s~erm binding site exposed outside the cell and which had another site inside the cell. This latter site was not active until the outer site bound the s~
I would like to thank Dr. David Sonneborn for pointing out the transduction aspect of Lillie's fertillzin model.
P,EFE REN CES I.
Sire, G., Yague, J., Nelson, J., Marrack, P., Palmer, E., Augustin, A., and Kappler, J. Primary structure of human T-cell receptor alpha chain. ~'ature 312, 771, 1984.
282
2.
CELL SURFACE RECEPTORS
Vol. IO, No. 2
Born, W., Yag~]e, J., Palmer, E., Kappler, J., and Marrack, P. Rearrangement of T-cell receptor beta-chain genes during T-cell development. Pro_cL_N_at~__A_ca_d.__S_c]~U_S_A82, 2925, 1985.
.
Ymrrack, P., Endres, R. Shimonkevitz, R., Zlotnik, A., Dialynas, D., Fitch, F., and Kappler, J. The major histocompatibility complexrestricted antigen receptor on T-cells. II. Role of the L3T4 product. J, Exp._ Med. 158, I077, 1983.
.
Swain, S.L., Dialynas, D.P., Fitch, F.W., and English, M. ~onoclor~l antibody to L3T4 blocks the function of T-cells specific for class 2 Eajor histocompatibility complex antigens. J~_Y~_~®_un_o~_._13_2,1118, 1984.
.
De~eish, A.G., Beverley, P.C.L., Clapham, P.R., Crawfcrd, D.H., Greaves, M.F., and Weiss, R.A. The CD4 (T4) antigen is an essential com;~nent of the receptor for the AIDS retrovirus, l~ature 312, 763, 1984.
.
Klatzmann, D., Champagne, E., Chamaret, S., Gruest, J., Guetard, D., Thierry, H., Gluckman, J.C., and Montagnier, L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 31_2, 767, 1984.
.
Fl~na~an, J. and Koch, T. Nature 273, 278, 1978.
.
Woda, B.A. and Woodin, M.B. The interaction of lymphocyte m ~ b r a n e proteins with the lymphocyte cytcskeletal matrix. _J~__I=T~9_u_n_ol_~_133,2767, 1984.
.
Coggeshall, K.M. and Cambier, J.C. B-cell activation VIII. N~mbrane immunoglobulins transduce signals via activation of phosphatidylinositol hydrolysis. J. I~__muD_o_lj_1_33,3382, 1984.
Cross-linked surface Ig attaches to actin.
10.
Yaffe, L.J. and Finkelman, F.D. Induction of B-lymphocyte receptor for T-cell replacing factor by crosslinking of surface IgD. _P_r99_.__N_a_t~_Ac~_d~ Sol USA 80, 293, 1983.
11.
Hadley, M.A., Byers, S.W., Suarez-Quian, C.A., Kleinman, H.K., and Dym, M. Extracellular matrix regulates Sertoli cell differentiation, testicular cord formation, and germ cell development in vltrQ. J,__Cg_l]~ Bio~_. 101, 1511, 1985.
12.
Solursh, M., Jensen, K.L., Zanetti, N.C., Linsenmeyer, T.F., and Reiter, R.S. Extracellular matrix mediates epithelial effects on chondrogenesis in v~tro. Devel~ Bilo_~j_jO~, 451, 1984.
13.
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