The C D 2 m olecule, a 50-55 K D a cell surface g ly c o p ro te in also k n o w n as T i l o r L F A 2 , is expressed on m ost T-cells and N K cells in m a n (V e rb i et aL, 1982) m ouse (A lte v o g t et aL, 1989; Yagita et aL, 1989) and ra t (W illia m s and Barclay et aL, 1987). M u rin e CD2 b u t n o t ra t o r h u m a n is also expressed on the surface o f pre-B and B-cells (Y agita et aL, 1989). The e xp ression o f the m u rin e C D2 gene is n o t detectable u n til e m b ry o n ic d a y 15 (O w e n et aL, 1988).
The C D2 p ro te in belongs to the im m u n o g lo b u lin s u p e rfa m ily an d consists o f the e xtra c e llu la r, transm em brane and cyto p la s m ic d o m a in s (B iere r and B u ra k o ff, 1989; D a v is and va n de M e rw e , 1996). The C D 2 m o le c u le is th o u g h t to be h e a v ily glycosylated and b in d s to the w id e ly expressed CD58 (or L F A 3 ) and CD59 lig a n ds as w e ll as to the CD48 m ole cu le expressed on leukocytes (D avis and va n de M e rw e , 1996).
E x p e rim e n ts u s in g m o n o c lo n a l a n tib o d ie s d ire c te d a g a in s t C D 2 have sh o w n th a t CD2 is in v o lv e d in T -cell adhesion and a c tiv a tio n (B iere r and B u ra k o ff, 1989; G o llo b et aL, 1995). W h e n s tim u la te d b y a p p ro p ria te m o n o c lo n a l antibo d ies (m A bs) o r a p a rtic u la r c o m b in a tio n o f an a n tib o d y and lig a n d , CD2 e licits p ro life ra tiv e responses com parable to those o f TCR m A b s (M euer et aL, 1984; H u n ig et aL, 1987; C la rk et aL, 1988). I t is th o u g h t th a t C D 2 s ig n a llin g is m e d ia te d b y the h ig h ly c o n se rve d c y to p la s m ic d o m a in w h ic h has been reported to associate w ith F yn, L c k and P I 3 kinases
(Bell et aL, 1996; C arm o et aL, 1993; S h im izu et aL, 1995). I t has been sh o w n th a t h u m a n C D 2 a n tig e n is fu n c tio n a l in tra n s g e n ic m ice in d ic a tin g a c o n s id e ra b le c o n s e rv a tio n o f th e C D 2 -m e d ia te d s ig n a l tra n s d u c in g processes betw een m an and mouse (M o n o s to ri et aL, 1991).
H o w e v e r, in s p ite o f th e la rg e b o d y o f e v id e n c e d e m o n s tra tin g an im p o rta n t ro le o f C D 2 in T -cell responses, the C D 2 k n o c k o u t e x p e rim e n t re su lte d in a h e a lth y m ouse w it h an a p p a re n tly n o rm a l im m u n e system , in d ic a tin g th a t the ro le o f C D 2 in T -c e ll b io lo g y is n o t in d is p e n s a b le (K ille e n et aL, 1992). H ow e ve r, it is possible th a t the real effects o f the loss o f CD2 expression re m a in undetected because th e y are sub tle a n d / o r have been concealed b y a d a p ta tio n d u r in g T -c e ll d e v e lo p m e n t in th e C D 2 m u ta n t m ice. F or exam ple, the C D 2 -lig a n d in te ra c tio n m a y a llo w lo w e r a ffin ity TCRs to be u tilis e d , thereby increasing the size o f the m a tu re T -cell re p e rto ire (D avis and va n de M e rw e , 1996). Thus, it has been s h o w n th a t the o verexpression o f the hC D 2 in transgenic m ice p ro fo u n d ly in flu e n ce s b o th T C R e x p re s s io n an d th e s u r v iv a l o f d e v e lo p in g th y m o c y te s , suggesting s ig n ific a n t cross-talk betw een CD2 and TCR w it h consequences fo r T -ce ll s tim u la tio n and d e velo p m en t (M e lto n et aL, 1996).
Gene S tru ctu re
The h u m a n CD2 gene is 14 kb lo n g and com prises fiv e exons. The fir s t exon (157 b p ) contains the 5 '-u n tra n s la te d re g io n and m o st o f the n u c le o tid e s encoding the signal peptide. Exon tw o (321 bp) and three (231 bp) de fine the e x tra c e llu la r d o m a in , exon fo u r (123 b p ) encodes the tra n s m e m b ra n e
d o m a in , w h e re a s exon fiv e (765 b p ) codes fo r v ir t u a lly the e n tire c y to p la s m ic d o m a in and the 3 '-u n tra n s la te d re g io n . The size o f the fo u r in tro n s are 0.77 kb, 3.3 kb, 2.9 kb, 3.9 kb. The m u rin e CD2 gene has a s im ila r o rg a n is a tio n w it h e x o n -in tro n b o u n d a rie s e s s e n tia lly id e n tic a l to the h u m a n gene (D ia m o n d et al., 1988; Lang et al., 1988).