Fcy Receptors Immunol Res 1992;11:217-225

Fcv Receptors: Gene Structure and Receptor Function

P. Mark Hogarth Mark D. Hulett Narin Osman Austin Research Institute, Kronheimer Building, Austin Hospital, Heidelberg, Vic.,Australia

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Key Words Fc receptor Receptor function Gene structure and regulation Protein

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Abstract Molecular studies of murine FcyR have revealed much exciting new information about the structure and regulation of FcTRI and FcTRII genes and of the Fcq,RI protein. The FcTRI gene is composed of six exons, whereas the Fcq,RII gene is composed of ten. The extracellular domains are encoded by individual exons in both genes (three in F ~ R I and two in FcTRII); however, the Fc~,RII gene shows greatest complexity in the region encoding the cytoplasmic tail and membrane spanning region, which is encoded by four exons compared to only one in the FcTRI gene. Expression of FcTRII is controlled by elements within the first 641 bases upstream of the transcription initiation site. The function of the domains of FcTRI has been defined with the surprising finding that in the absence of the third domain the first two extracellular domains function as a broadly specific low affinity Fc'/RII-like receptor. o . . e . ~

Introduction The last 5 years has seen remarkable advances in our understanding of the structure and function o f Fc receptors (FcR) and their genes. The IgG receptors (Fc3,R) have been studied in detail and are now recognised as a family of homologous but distinct proteins in both man and mouse [ 1-6].

There are three classes of Fcq,R in the mouse, FcTRI, FcTRII and FcTRIII (formerly called ctFcyRII), which are homologous but have distinct structural differences [1-4, 7]. The principle regions of homology are the extracellular Ig interactive domains of which the low affinity FcTRII and Fcq,RIII have two, as does the high affinity IgE receptor Fc~RI. FcaRI is unique in that it has three extracellu-

Dr. P. Mark Hogarth Austin Research Institute Kronheimer Building, Austin Hospital Burgundy Street Heidelberg, Vic. 3084 (Australia)

9 S. KargerAG, Basel 0257-277X/92! 0114-021752.75/0

lar domains, the first two domains being homologous to those of the low affinity receptors but the third domain is unique [1-4, 7]. The regions of greatest difference between these FcTR are the membrane-spanning regions or cytoplasmic tails, i.e. the signal transduction region. Indeed even in the two FcTRII isoforms (131 FcTRII and 132 FcTRII), the only sequence difference lies in their cytoplasmic tails wherein 132 FcTRII has a 46 amino acid deletion [2, 3]. Clearly the identification of the structure and regulation of the FcTR genes and a knowledge of the functions of the domains of the FcTR proteins will establish a biochemical basis for the extensive biological roles of these receptors [8, 9]. In this report we examine the structure and regulation of FcTRII and Fc'/RI genes of the mouse and identify the function of FcR protein domains.

Materials and Methods Isolation of Genornic Clones Genomic clones were isolated from ~.EMBL3 or ~. Charon 4A libraries (BALB/c embryonic or T-cell lymphoma) using 32p-labelled FcTRI or FcTRII full-length cDNA probes as described [10]. Sequencing was performed by the dideoxy technique and all restriction mapping, bybridisations and Southern blotting performed by standard techniques [ 11 ].

CA T Assays Three genomic segments as indicated in the text were amplified by polymerase chain reaction (PCR) [12] to yield 3 fragments extending from 105, 395 and 641 bases, respectively, upstream of the transcription initiation site, to the same position 73 bases downstream (positions based on the sequence as published) [10]. The primers for the PCR were derived from the published sequence [10] and each of the upstream primers (- 105, - 395, - 641) had an additional HindlII site added at the 5' end and the downstream primer (+ 73) had a Sail site added. The amplified fragments were digested with Hindlll and Sail and cloned into the HindlIl and Sail sites of pCAT-basic vector which

218

contains the CAT structural gene but no promotor or enhancer elements (Promega). Transfection of the constructs into monolayers of COS cells was performed using the DEAE-dextran method [13] and CAT activity measured as described [ 14]. Controls for the assays included cells transfected with pCAT-enhancer plasmid (CAT gene lacking promotor but containing enhancer), pCAT-promotor (CAT gene plus promotor but no enhancer) pCATcontrol (CAT gene plus promotor and enhancer;, Promega).

Construction and Expression of Chimaeric Receptors Two chimaeric FcTR were produced containing: (i)the first two extraeellular domains of Fc~RI attached to the transmembrane and cytoplasmic tail of FcTRII. and (ii) the extracellular domains of FeTRII attached to the third domain, transmembrane and cytoplasmic tail or FcTRI. The exchange of regions made use of a Sail site in polylinkers of the vectors pKC3 or pKC4 [15] and an endogenous Apal site in the FcTRII eDNA encoding the membrane proximal region between the extracellular domains and the transmembrane/cytoplasmic tail [4]. The Fcq,RII cDNA was cloned into the Pstl site (adjacent to a SalI site) ofpKC3 and pKC4 [15] which results in the presence of theSall site at the 5" or 3' end of the inserted eDNA in pKC3 or pKC4, respectively. The regions of FcTRII to be replaced by corresponding regions of FcTRI were removed after digestion with Sail and Apal. The Fc'/RI regions to be cloned into the Sail/ Apal-digested pKC-FcTRII plasmids were generated by two PCR amplifications of FcTRI cDNA [7]. First. the leader and the first two domains were amplified using a 5' primer with a Sail site and a 3' primer containing the sequence GGGCCC which introduces an ApaI site into FcTRI eDNA between domains 2 and 3 in the position that corresponds to that in FcTRII. Second, sequences, encoding the third domain, transmembrane and cytoplasmic tail were amplified using a 5' primer that introduces the Apal site and a 3' primer that contains the SalI site. The amplified products were digested and cloned into the appropriate Sail/ Apal-digested pKC-FcTRII plasmid to generate pKC3FcRI/II containing the first two domains of Fc3,RI attached to the transmembrane and cytoplasmic regions, and pKC4-FcRII/I containing the extracellular domains of FcTRII attached to the third domain, transmembrane and cytoplasmic region of FcTRI. Oligonucleotide sequences used in PCR reactions were: (1) for the domain 1 and 2 FcTRI fragment, 5' TTTGTCGACATCATTCTTACCAGCTTTGGAG-

Hoganh/Hulett/Osman

Fcy Receptors

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2

3

4

5

6

7

8

9

10

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1

2

3

4

5

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Fig. 1. Structure of FcyRII and FcTRI genes. Exons are numbered on top. Open boxes indicate untranslated regions, and shaded boxes coding sequences. Transcription initiation indicated by the arrows. (Not to scale.)

ATG 3" and 5" GGTGAAGGGCCCTTTCACCGTGATGG 3', and (2)for the domain 3, TM and CT FcTRI fragment, 5' GGTGAAAGGGCCCTTCACCACGCCAG 3' and 5" TTTGTCGACCCGGGGATCCTCTAGAGTCGAC 3'.

Scatchard Analysis Assays were performed on COS-7 cells transiently transfected with FcR expression constructs (above) 48 h after transfection using ~251-1abelled IgG2a, as described [7].

Tran+~,ction of Chimaeric cDNA COS-7 cells were transiently transfected as monolayers in Petri dishes with FcR cDNA expression constructs by the DEAE-dextran method as described previously [ 13].

Detection of FcTR Expression by Erythrocyte-Antibody Rosetting COS-7 cell monolayers, 48 h after transfection, were incubated with erythrocyte-antibody complexes in rosetting assays as described previously [16]. Erythrocyte-antibody complexes were prepared by sensitising sheep red blood cells with rabbit anti-sheep red blood cell IgG, or by coating sheep red blood cells with trinitrobenzene sulphonic acid and sensitising these cells with anti-trinitrobenzene sulphonic acid isotypespecific monoclonal antibodies as described [ 17].

Results and Discussion

FcTR Gene Structure Our recent genomic cloning experiments have defined the structure of mouse Fcq,R genes. Isolation and characterisation of genomic clones from genomic ~. libraries has revealed that the F~RII gene spans approximately 18 kb of DNA on chromosome 1 [I 0]. The gene was characterised from 1 kb upstream from the transcription start site to just downstream of the adenylation signal of the mRNA (fig. I). Ten exons encode the mature [31 mRNA [4, 10]. Exons 1,2, 3 and 4 encode the 5' untranslated region (UTR) and then leader sequence as well as the amino terminal Thr residue of the mature F~RII protein (fig. 1). Like most members of the Ig superfamily, the individual extracellular Ig-binding domains are encoded by single exons (exons 5, 6) as is the membrane anchoring sequence (exon 7). The cytoplasmic tail of the F ~ R I I is encoded by a series ofexons, (exons 8, 9, 10) and this is the most distinctive feature of the gene when compared to other FcR genes which encode the membrane-spanning region and 3" UTR in only one exon. Furthermore, the two

219

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Fig. 2. Structure of the 5'end of the FcI,RII gene extending from 1,963 bases upstream of the transcription initiation site to 7,366 bases downstream [I0]. Exons are numbered open boxes. Various sequence elements of interest are indicated: Spl = site for binding of Spl transcription factor;, Repeats = overlapping tandem repeat; M = site of methylation; GRE = glucocorticoid response element; AP4 = site for binding of AP4 transcription factor. Positions of features, relative to the transcription start site, are numbered in parentheses. The transcription start site is indicated by the horizontal arrow and marked as position +1. All upstream positions indicated by -, and all downstream by +.

mRNA transcripts ([31 Fc'/RII, 1~2 FcyRII) arise by alternate splicing of exon 8. Indeed this gene is the only FcR gene to actively produce alternate mRNA transcripts [6, 10, 17]. The structure of the F ~ R I gene is less like the FcTRII gene and more closely resembles that of the FcTRIII and FceRI genes (fig. 1). The Fc'/RI gene is composed of 6 exons within a 9-kb stretch of DNA. The 5" UTR and leader sequences are encoded by exons 1 and 2, with exon 2 composed of only 21 bp encoding the hydrophobic core of the leader sequence, which is typical of all FcTR genes [6, 10, 17]. The three extracellular domains of Fc),RI are encoded by single exons whereas the transmembrane region, cytoplasmic tail and 3"UTR have the typical FcR gene configuration and are all encoded by one exon (fig. 1).

Regulation of FcyRH Expression The 5" end of the mouse Fcq'RII gene contains a number of sequence motifs that are clearly identical or homologous to elements that are known to regulate the expression of

220

eukaryotic genes and may be involved in the regulation of the FcTRII gene. Sequence analysis of the region extending upstream from the transcription initiation (TI) site (base position +1) to position - 1,963 has identified several regulatory-like elements (fig. 2). Whilst no CAAT or TATA boxes were evident three GC box (GGGCGGG) sites tbr the binding of the Spl transcription factor [18] were evident 883 and 1,963 bases upstream of the TI site. GC boxes have been identified in a number of eukaryotic genes and a number of genes of the lg superfamily that lack a TATA or CAAT boxes like the Thy-I gene [19]. The sequence motif (CAGCTTGG) homologous to that recognised by the AP-4 transcription factor was identified 124 bp upstream of the TI site as were two glucocorticoid-responselike elements found 142 and 171 bp from the TI site as well as an overlapping direct repeat (TACCCTGGGC TA CCCTACCCTA) at position -333 (fig. 2) [10]. Finally, since we have shown that methylation of the FcTRII gene effects its expression, the sequencing ofthese genes was able to iden-

Hogarth/Hulett/Osman

Fc7 Receptors

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Fig. 3. Regulation of CAT gene activity by 5' sequences of the 13Fc't'RIl gene. Chromatogram of acetylation products of chloramphenacol after incubation of lysates derived from cells transfected with CAT gene constructs under the control of various elements as follows: 105, 395, and 46 l = genomic segments of the FcyRII gene 105, 395, and 461 bases upstream of the transcription initiation site; P - E - = CAT gene lacking promotor and enhancer, P-E + = CAT gene lacking a promotor but containing an enhancer, P+E- = CAT gene containing a promotor but lacking an enhancer: P+E + = CAT gene containing both a promotor and enhancer; cells = untransfected cells.

tify three methylation-sensitive HpalI sites (CCGG) known to require demethylation for Fcq'RII expression. The three sites occur at: (i) 306 bp upstream of the TI site between the direct repeats and the glucocorticoid-response-like elements (fig. 2); (ii) at the splice acceptor site of exon 3, and (iii)within the large intron separating exons 3 and 4. Since the precise roles of these elements in the FcTRII gene is somewhat speculative, we examined the capacity of the 5' end of the gene to drive transcription of a CAT reporter gene (fig. 3). A set of three nested regions was prepared extending from 105, 395 or 641 bases upstream of the TI site to 73 bases downstream, within exon 1 encoding the 5'UTR of the Fc't'RII gene (fig. 2). These regions of the FcTRII gene varied in their capacity to drive

transcription of the CAT reporter gene when transfected into COS cells. The shortest region analysed (-105 to -173) failed to drive transcription of the CAT gene even though this region contained the most 3' GC box, clearly indicating that this region alone is not sufficient for transcription of the gene. The two larger regions examined (-395 to +73 a n d - 6 4 1 t o - 1 7 3 ) both enabled CAT gene transcription but at varying levels of activity. The greatest CAT activity was obtained with the largest FcTRII gene segment (-641 to +73). Both -641 to+73 and -395 to +73 contain the Spl and AP4 elements as well as the tandem glucocorticoid-response-like elements, the direct repeats and a methylationsensitive site. However, it is clear that the additional 246 nucleotides of upstream sequence found in the -641 to + 73 segment sig-

221

Table 1. Specificity of chimaeric Fc receptors

Receptor

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nificantly increases the level of CAT gene transcription compared to that obtained with the -395 to +73 gene segment (fig. 3). These results imply that at least 641 bp of upstream sequence are required for maximum gene expression under these conditions. However, the precise roles of each of the putative regulatory elements within this region remain to be determined as do the factors that regulate tissue-specific expression of FcTRII found within the haemopoietic lineage.

Identification of Functional Domains of FcTRII and FcTRI The cloning of mouse Fc'fRI and F ~ R I I has indicated that both receptors are unique but structurally related molecules. They are members of the Ig superfamily, containing extracellular regions comprising Ig-like domains of the C2 set [20]. FcTR! contains three such domains, whereas FcTRII contains two, which exhibit marked homology with the first two domains of FcTRI (46 % amino acid identity). However, the two receptors have functionally distinct IgG-binding characteristics. FcTRI is a high affinity receptor which binds only IgG2a, in contrast to FcTRII which has a broader specificity binding IgG1 IgG2a and

222

IgG2b, however, with low affinity. The homology of the first two domains of Fc'/RI to those of FcTRII suggest that the third domain of Fc3,RII may be responsible for the unique Igbinding properties of FcTRI. In order to assess the roles of the extracellular domains of FcTRI in Ig binding, chimaeric receptors between FcTRI and FcTRII were generated by exchanging the first two domains of FcTRI with the homologous counterparts of FcTRII. Two chimaeric FcR were generated; pKC3-FcTRI/II which contained the first two domains of the high affinity FcTRI linked to the transmembrane and cytoplasmic region of FcTRII; pkC4-FcTRII/I contained the first two domains of FcTRII attached to domain 3 and the membrane-spanning region and cytoplasmic tail of FcTRI. The chimaeric receptors were expressed in COS-7 cells using a transient system, and their IgG-binding characteristics assessed, the specificity of Ig binding through the ability to bind immune complexes of specific IgG subclass, and the affinity of Ig binding through Scatchard analysis with monomeric Ig (table 1). COS-7 cells expressing FcTRI/II or FcTRII/I were able to bind rabbit IgG im-

Hogarth/Hulett/Osman

Fc7 Receptors

mune complexes whereas mock transfected cells could not, indicating that both chimaeric receptors have the capacity to bind IgG and are thus functional cell surface Fc-binding proteins. Therefore, domains 1 and 2 of FcTRI are able to bind Ig when not associated with domain 3. The FcTRII/I chimaera bound murine IgGl and IgG2a complexes, indicating that the specificity of Fcq,RII (imparted by domains 1 and 2 of FcTRII) was retained, domain 3 having no influence on the specificity of IgG binding. The FcTRI-II chimaera containing only domains 1 and 2 of FcTRI was surprisingly found to have the same specificity of IgG binding as FcTRII, being able to bind murine IgGl and IgG2a complexes. Thus removal of domain 3 from FcTRI in generating the FcyRI-II chimaera resulted in the broadening of the specificity for IgG by domain 1 and 2 of FcTRI, in effect FcyRI was converted to an FcTRII- 'like' receptor. The affinity for monomeric IgG of both chimaeric receptors was essentially undetectable as for the low affinity receptor FcTRII, in comparison to the high affinity receptor FcTRI which had an affinity of 5 • 10 7 M -I. These results indicate that the chimaeric receptors exhibit low affinity IgG binding. Thus domains 1 and 2 of FcTRI are unable to bind IgG with high affinity when not associated with domain 3. Also high affinity IgG binding of FcTRII was not able to be generated by linking domain 3 of FcTRI to domains 1 and 2 of FcTRII. These results suggest that all three domains of FcyRI are required for the formation of a structural conformation necessary for the specific high affinity binding of IgG2a.

Evolution of FcR Genes The identification and characterisation of FcR genes and proteins described herein and by others provide an indication of the history

of the development of the FcR gene family, and also provide one of the few examples of experimental evidence of how Ig superfamily members evolved (fig. 4). The relationship between FceRI and other FcR is clear. From nucleic and amino acid sequence data it is obvious that the high affinity IgE receptor FceRI and the IgG receptors are related [21,22]. The extracellular domains of Fc8RI and FcTRII are almost identical in size and show approximately 43 % amino acid identity, and the transmembrane region of Fc8RI is highly homologous to FcTRIII but distinct from that of FcTRII [2 l, 22]. Furthermore, the overall structure of the FceRI gene is most similar to that of FcTRIII, i.e. a single exon for each extracellular domain and one exon that entirely encodes the transmembrane, cytoplasmic and 3' UTR. It should also be noted that the configuration of a single exon encoding the membrane, cytoplasmic and 3' UTR is also common to FcTRI and FcTRIII. Thus it is likely that the FceRI gene arose by a duplication of the primordial receptor gene (fig. 4, arrow 1). The primordial or early FcTR gene then underwent diversification by different mechanisms, some of which are clearly identifiable. FcTRIII is likely to be the earliest FcTR and has undergone least change compared to FcTRI and FcTRII (fig. 4, arrow 2). The homology of FcTRIII to FceRI and their similar gene structure are obvious and have been discussed above, although it should be noted that in man the FcTRIII gene has also been further duplicated and mutated to encode an additional phosphoinositol-anchored form of FcyRIII. As a result of the work with the chimaeric Fc~RI/FcTRII molecules and the cloning of FcTRI cDNA and genes, it is now clear that the FcTRI gene arose by the simple insertion of an exon (of Ig-like origin) into the early FcTRIII gene. This is clearly the case as: (i) re-

223

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T C U

L

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L

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Fig. 4. Evolution of FcR genes. Exons are indicated by boxes. Not all 5" exons are shown for clarity. Related exons indicated by similar shading. L = Leader: D I = d o m a i n 1; D2 = domain 2; D3 = domain 3; T = transmembrane; C = cytoplasmic tail: U = untranslated region. N u m b e r e d arrows indicate events detailed in text.

moval of the third domain from FcTRI converts this receptor to a broadly specific low affinity FcTR, the low affinity phenotype could be either FcTRII or FcTRIII-like since these are indistinguishable in the mouse where FcTRII and FcTRIII (aFcTRII) share > 90% amino acid identity and show identical specificity; (ii) the membrane-spanning region of FcTRI (WFHILFYLSVGIMFSLNIVLYVE[7]) has some, albeit weak, homology to that of FcTRII (WYHTAFSLVMCLL_FAVDTGLYFV[2], and (iii)the overall gene configuration (except for the inserted exon) is similar to FcTRIII and FceRI (fig. 4, arrow 3). Finally, FcTRII is the most distantly related of the IgG receptors (fig. 4, arrow 4).

224

Considerable amino acid identity exists between the extracellular domains of murine F ~ R I I and FcTRIII ( > 9 0 % ) and FcTRI (45%). However, there has been extensive diversification and specialisation of the transmembrane, cytoplasmic, and 3" U T R wherein 4 exons subserve this function compared to a single exon of the other FcTRI, FcTRIII and FcsRI genes (fig. 4). It is also noteworthy that human FcTRII genes have undergone further duplication to yield at least three FcTRII genes [6]. Clearly, there have been a series of duplications and mutations to generate the range of receptors that have been identified to date, b u t t h e most striking observation is that the first two domains of the high affinity receptor

Hogarth/Hulett/Osman

Fc7 Receptors

Conclusion

in fact behave like a low affinity receptor and that the third domain suppresses this intrinsic ability. Taken together with the data showing that the third domain is encoded by a single exon these findings are functional evidence of the evolution of the Ig superfamily as proposed by Williams and Barclay [20]. The modification of protein function by the acquisition of Ig-like domains (and the Ig-like exon) is clearly the case in FcTRI.

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References 1 Hibbs ML, Walker ID, Kirszbaum L, Pietersz GA, Deacon N J, Chambers GW, McKenzie IFC, Hogarth PM: The murine Fc receptor for immunoglobulin: Purification, partial amino acid sequence and isolation ofcDNA clones. Proc Natl Acad Sci USA 1986;83:6980-6984. 2 Ravetch JV, Luster AD, Weinshank R, Kochan J, Pavolec A, Portnoy DA; Hulmes J, Pan YCE, Unkeless JC: Structural heterogeneity and functional domains of murine immunoglobulin G Fc receptors. Science 1986:234:718-725. 3 Lewis VA. Koch T, Plutner H, Mellman I: A complementary DNA clone for a mucrophage-lymphocyte Fc receptor. Nature 1986;324:372375. 4 Hogarth PM, Hibbs ML, Bonadonna L, Scott BM, Witort E, Pietersz GA, McKenzie IFC: The mouse Fc receptor for lgG (Lyl7): molecular cloning and specificity. Immunogenetics 1987;26:161-168. 5 Brooks D, Qui WQ, Luster AD, Ravetch J: Structure and expression of human IgG FcTRII (CD23): Functional heterogeneity is encoded by the alternately spliced products of multiple genes. J Exp Med 1989; 170:1369-1385. 6 Qiu WQ, de Bruin D, Browastein BH, Pease R, Rabetch JV: Organization of human and low-affinity FcTR genes: Duplication and recombination. Science 1990;248:732735.

7 Sears DW, Osman N, Tate B, McKenzie IFC, Hogarth PM: Molecules cloning and expression of a mouse high affinity Fc receptor for IgG. J Immunol 1990;144:371-378. 8 Mellman I, Koch T, Healey G, Hunziker W, Lweis VA, Plutner H, Miettinen H, Vaux D, Moore K, Stuart S: Structure and function of Fc receptors on macrophages and lymphocytes. Cell Sci 1988;9(suppl):45-65. 9 Unkeless JC, Scighano E, Freedman VH: Structure and function of human and murine receptors for IgG. Annu Rev Immunol 1988;6:251281. 10 Hogarth PM. Witort E, Hulett MD, Bonnerot C, Even J, Fridman WH, McKenzie IFC: Structure of the mouse 13Fc3,receptor II gene. J lmmunol 1991 ; 146:369-376. 11 ManiatisTE, Fritsch F, SambrookJ: Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, Cold Spring Harbor Laboratory, 1989. I2 Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA: Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988;239:487491. 13 Seed B, Aruffo A: Molecular cloning of the CD2 antigen, the T cell erythrocyte receptor, by a rapid immunoselection procedure. Proc Natl Acad Sci USA 1987;84:3365-3369. 14 Rosenthal N: Identification of regulatory elements of cloned genes with functional assays. Methods Enzytool 1987;152:704-720.

15 Van Doren KD, Hanahan D, Glutzman Y: Infection of eukaryotic cells by helper-independent recombinant aden 9 Early region I is not obligatory for integration of viral DNA. J Virol 1984;50:606-614. 16 Parish CR, Hayward JA: The lymphocyte surface I. Relationship between Fc receptors, C3 receptor and surface immunoglobulin. Proc R Soc Lond 1974;187:47-63. 17 Kulczycki A, Weber J, Spares HA, Onken MD, Thompson JA, Chaplin DD, Loh DY, Tillinghast JP: Genomic organization of mouse Fc3' receptor genes. 1990;87:2856-2860. 18 Kadonaga J, Jones KA, tan R J: Promotor specific activation of RNA polymeruse II transcription by Spl. TIBS 1986: I 1:20-23. 19 Gigvere V, Is 9 K-I, Grosveld F: Structure of the murine Thy-I gene. EMBO J 1985;4:2017-2023. 20 Williams AF, Barclay AN: The immunoglobulin superfamily: Domain for cell surface recognition. Annu Rev Immunol 1988;6:381-405. 21 Shimizu A, Tepler I, Benfey PN, Berenstein EN, Siraganian RP, Leder P: Human and rat mast cell high affinity immunoglobulin E receptor: Characterization of putative ct chain products. Proc Natl Acad Sci USA 1988;85:1907-1911. 22 Chisel R, Jouvin MHE, Kinet JP: Complete structure of the mouse mast cell receptor for IgE (FcTRI) and expression of chimaeric receptors (rat-mouse-human) on transfectec cells. J Biol Chem 1989;264: 15323-15327.

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Fc gamma receptors: gene structure and receptor function.

Molecular studies of murine Fc gamma R have revealed much exciting new information about the structure and regulation of Fc gamma RI and Fc gamma RII ...
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