26

~raclpltata formed by an antibody and Its pmctpltln, at well tr6 In that

farmed by an arntltbody ad the prselgltln to nom& ~1obuIln.  In agrement vlth
             40
thla, %ith aad Warrai&  found that B preclpitatsr farmed by I pruclpitln an4

w  2'. C, Smith pnnd J, Harnrck, Br%t. J. IExr!. plpth. & 494 (lgp).

a ~emm contslnlng dlphtherta antitoxIn baa the powtm of oolabining 14th

Bsldalberg;ss tana      41
           Treff8rr  Sn the C&de of apauiflc pra4lpltatsr f0rtasa by

pnausaowana antfbody with homolo~us antlaerm.

*
8  Pa&   A ct                           t 8 3 clflei rri

&&,&4&g,--In order that an antibody be sffecflror, the mxft~cb region of the

anti-n covered by an mtibodq end nnrst be dirge emou&h uo that the lntsggated

With n bond of awmqo &ran&h the aurtfbody saleoala till bs dlsmfatsd fram

Its antlpm temglatcr, per&ape with ths aid of the auxiliary meahaalmn mentioned

in Ssctlan VI, taut11 an a@llbrlum or rtemdy-skts conamtratlon lr iraiIt u$

In the serum,  Mow If the antigen mrface aantainr a large aolm'ber of strong

#Pqm, capahlr of intcmatlxv! rtmdgly with oosp1mmntar.y rtmzturss In the

aurtibody, tha antlbodpa&Idfan bond IIPB;P bs so rtroap; that the antibody Is not

out by sxpsrlm8nt.  Thou a blmd protaln such a+ agir. calbumin Is a good antfgatn,

am are srlso 6Ott$X@bt8d prot&mt with we& groups attwhsd. b& amprotein with

many strong groups attmhad (arsmnla BIcid, sulfonl~ lacld, alto, eta; the aso
ggw.q ltsrlf irr a r&her strong group, CspeBls of fonalng hydrogen bom3a) IS


a poor antigen; ln ordw to obtain oerus to such haptana an amproteln contalnlng

a llmltsd nrmbsr of the gmutpr laaat be used.  I am told by Dr. landsteinelz that

this obssmtion was lasds In the early days of %he study of rzopotelne 42
                                                                           .

" See K, 3.6mdatalner and R, La&,

Pertinent data hare been reported ia reaent yeam by Haurowitz and hlr
uollaboratorr (a.*.), wha found ths crptlmum arsenlu content for the prodaatlun
of antlhapten bg amprotein s\ade from areanilla acid to be between 0.5 and l.C$;

wry little antibody la prodwed by antigens with over 2$ wwmla, althou& stzvng
preclpl~kln reaction is shown by azoprotsin tith racy lammla oonWmt am grclgt as 1%

  A ?HM?o~~ dedtmtion, relatl~ to speclflelt;r, CNLXI also be made. To aohle~e

a saff lolently rtraa@ aat lbabat Igem bona with an antigen aantainlng only w4mk

groupe a large fuurfme raglan of #a antigen mast mm8 Into play, wIuwemr vlth
an antigen oontaining rtrcmg grmpr only a small mglon (in the lilait OZTO group)

Is needed.  Izr6nc~ kthibaab.30 to 6mdmat m m-0% m aihow 1~
                                                                         --
rpwlfiottg, md those to mtigena contalnfng weak puprr bow j&&
              ---             apr, clficitg.

This ~radirrtlon lr eubstautiated bg nmny obssmtlanr. k albmtln, hemg3obln.

and ~lmllar protelnr &Ire hi&w spaclfla 16z-a~ wkerear srroproteinrr produae sera

whluh are lesa lQ,eOifftt,, rtramg awm-rem&lone being &me- mood: mu'lonr

protslnr with the qpa hapten attached.  ThIr altows, Inbad, that a aln&le

bapten amup glres a rufflelsntly rtrong bond to held antibody and antigen

togather.  Xn Buch a emme the appr&~tlon of the antibody to a strong hapten

lo very close, and great specslfllclty le sImwn 4th regard to the hapten Itself,

this upeolf lclty ImIng the grad ew the rtronger the hapten.  Nany emuplea of

theas offsets are to be fcnmd in Landrtainer'o work.

P___,-We nsxde the fundmerntsl portulate that the
.

end yartr of the polypeptlde &aina of the .@oImlln sao1euul.e are ohwaatwirsd

by having a rsry large nmiber of acamsible eonfle;rrm.tfoar with nearly tha taut


It Is mfmrdSngZy pmbab3.e the4 the en4 configurattons, &ring c-?xm.ctsfistla

gmymrtiae to the antlbodles, aronld be destwpd befora the central. pm-t of

the lao~tie la affeated and, Iitmeov%~, that t&a nmeiti~t~ ta danntaufng age&r

or crmtitfons of a.atibadier to differmt antlgene vmld be biffsmmt.  'Eh+

Isme mwwarke my "CM mx.de regw-dlng the dlfferenae In behmlor of anti-

antIbody mleculer coaa,*limmtarg to these rcaglonr Wul ridsin the power af

comblnlng with thm, ~erazae the snt3body imleat&!m coqlaaQ&ta~ to the reglanr

the bottosl ef the bottom 3.a~~' vm3d et111 !a aff@CtiW after the -~~rtlal

dawMam&ion of the aaolsmI8 by the m3.wfini-; of the layers, whereas the

antigenlo reglmm at th8 eider of the arlglnal laolecwle weld in large peVt

the ability to cmblae with WXti-@~~b m&bit swmm is met elqly

eqtlnined by the seew@tfonr that the natire a= alb'win 1m1ecu&e hae the b~@S

structure mqgeetad above and that th8 proa@SS of smYaa6 tlemtwration of thir


3 F Daaidli, H. Xkalelli, and 3. R. %darra&, Britl& J. Jkp, Path.
39j 6938).

  Rothen and Zkndsteinar (loa.*.) bars paintsd out that from thsae faotr
rqardirg uurfaue dmaturatian the conc~ualon an bs draM that "the srpecifis
reaalti+fty of antibudtss is w 8, hhra;s cmtent dupendent rtpan atruuture8
Iliffareat frwm thoas which resWly detsmine the upecifl&!Lty of antfgens*.

An interestiq poasiblm mMmI of pr@mAng antibodies front WWUIB or

globulin solution uutride of thrr anlti is inagsartsd by the theery. Tha, globulin

would be trutcrd tith 8 denat- agent or condition dffulmMy strong to oause

slowly tile mtigen or haptan ir premt ia the eelutfcm in eonsfdrsrable

aancantratiun.  The uhafn endr wmild then call up ta aumme the aanff$umtiuaa

stable tzn&az, these eond%tionr, uMc& wmzld be conffgum&lanr cumplswntary to

thocm of the a.ntigm or hapten.

Maay of the erapsrljsentu aqgpstsd abortl are befry undestaksn in uur

Laburatarirsr, with th8 collabaratioY3 af QT. Ddur c7aaqMll.

`hm is little bwir far sugtpZsrtin;CT porsfbls sneoharhm fur this ~rotmo at present.


into opsration in ths adl to frscilitatr the remwal of the antibody from tha

of I&I%& could uombine tith additiaml antigmi,


                Ifr




aomar8ationr with Dr. &Pl

ta hitP', ad ta acknovlsdg6 my


Pig. 1.

ng. 2.

Fig:. k

Fig. 5.

ng. 6.

Pk. 7.

Pig. 8.

h portion of un Pnt~body-antigen nstwork fomed in the Fe&on of

antib#Ay ext!te6L9.

A portion of the network forra,d in the region of antigaa w1w88.

Bspmsftntative 8olubla compluxes forma& vith QX@OI)II aatfgea,

A rolvble ucmplex form& with mumas ant%body.

The foldiag of yolypqtide &aim into a Zamr held together lx$

lnfno-oarbony hytIro&m bandr.