|
Items in cart [4] |
Questions? Call 888-624-8373 |
| ||||||||||||
| Copyright © 2009. National Academy of Sciences. All rights reserved. Terms of Use and Privacy Statement |
Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 160
OCR for page 161
ALFRED NISONOFF
January 26, 1 923-March 12, 2001
BY LISA A. STEINER, KATHERINE L. KNIGHT
AND ]. D O NALD CAPRA
AEFRED NISONOFF, WHO DIED on March ~ 2, 2001, was a ma-
jor contributor to many basic aspects of immunology
throughout his career. In aciclition to funciamental work
that helpecl to define the nature of antibodies en cl the genes
encocling them, he was an astute critic with penetrating
analytical skills. His monograph The Antibody Molecule
stancis as the clefinitive reference work on the subject to
1975, the time of its publication.
NisonofEs parents immigrated to the New York area from
Hungary en cl Russia as teenagers. Al was born in Corona on
January 26, 1923. When he was about two years oicI, his
parents movecl into a working-cIass, largely immigrant com-
munity in South River, New Jersey, to join other family mem-
bers. They operates! a kosher butcher shop en c! grocery
store. Al's parents had little formal education and his ini-
tial exposure to books en cl reacting was in school, where his
exceptional intelligence was soon recognized. At age 6 he
founcl himself in third gracle, en cl by 15 he hacl gracluatecl
from high school. One of the few students in his school to
go to college, Al receiver! a state scholarship en c! enrollee!
at Rutgers, which was within hitchhiking distance en cl al-
lowocl him to live at home. He became interested in chem-
161
OCR for page 162
62
B I O G RA P H I C A L
EMOIRS
istry when a high-school frienc! gave him access to his home
laboratory, en cl cleciclecl to major in this fielcI. It also seemed
to offer opportunities for practical future employment.
Upon graduation from Rutgers in 1942 at age 19, Al set
off in a Moclel A Forcl to take up a job with the U.S. Rubber
Company in Detroit. It was the first time he hacl been more
than 50 miles from home. He later recallec! being toic! by
an upper management person that he shouIcl be prowl
because U.S. Rubber clicl not orclinarily hire Jews. He was
probably not surpriser! to hear this, because it was generally
accepted at this time that many chemical companies wouIcl
not hire Jews (see Dan A. Oren, Joining the Club: A History
of Jews en c! Yale, p. 357, footnote 28. New Haven: Yale
University Press, 1985~.
Although Al was assigned to a fairly routine task, testing
various latex compounds for their ability to adhere to the
nylon coral required to strengthen airplane tires, he soon
macle a critical observation that changecl the procluction of
these tires so important for the war effort. One clay while
walking through the plant, he stopped to watch the con-
struction of self-sealing gasoline tanks macle from rubber
and strengthened with nylon cord dipped in a water-based
latex adhesive. Combining the keen power of observation
en cl imagination that was to characterize his future research,
Al aciaptec! this process to the problem of adhering nylon
coral to rubber tires so U.S. Rubber was launchecl into
making nylon-beltecl tires. Describing this practical cliscov-
ery many years later, Al with typical self-deprecation said it
was "primitive stuff . . . a mincIless sort of thing." Another
significant event of the time in Detroit was that Al met
Sarah (Sally) Weiseman at a Jewish community center. They
corresponclecl through the war years en cl were married im-
mecliately after his discharge from the Navy.
By 1943, with the war raging, Al became anxious to join
OCR for page 163
ALFRED NISONOFF
163
the armec! forces. Even though he hac! an occupational cle-
ferment, he enlistecl as a midshipman in the Navy. He served
until the end of the war, missing the invasion of Okinawa
only because his ship clevelopec! an engine problem. He
hacl not given much thought to the future, but a college
friend whom he met while passing through San Diego toIcl
him about the G.I. Bill, en c! he cleciclec! to pursue graduate
work in chemistry. He was clischargecl from the Navy in July
1946 en cl entered graduate school at Johns Hopkins Uni-
versity in September, receiving his M.A. in 1948 en c! Ph.D.
in 1951. His research, supervised by Frederick W. Barnes,
fir., was on the enzymatic mechanism of transamination.
Following graduate school en c! on the strength of his
previous success at U. S. Rubber, Al joined a branch of the
same company in Naugatuck, Connecticut. After two years,
however, he cleciclec! to return to work relater! to biochem-
istry en cl took a position with David Pressman's group at
the Roswell Park Memorial Institute in Buffalo, beginning
work that set the direction for much of his research in the
remainder of his career.
In the early 1940s David Pressman, then working in Linus
PauTing's group, carrier! out an extensive series of experi-
ments exploring the specificity of antibodies clirectecl against
haptenic determinants. These studies introclucecl the tech-
nique of quantitative hapten inhibition, an important ex-
tension of the experimental approach pioneered by Karl
Lancisteiner. Throughout his career Nisonoff appliecl quan-
titative approaches, often with anti-hapten antibodies, to a
number of problems in immunology. With Pressman, Nisonoff
explorecl the heterogeneity in the bincling of antibodies
with haptens en c! introclucec! means of estimating this het-
erogeneity quantitatively. In an important paper from this
period he clemonstratecl that the two combining sites on a
single antibody molecule have the same specificity. This
OCR for page 164
64
B I O G RA P H I C A L
EMOIRS
result, which confirmed! earlier experiments by Lancisteiner,
Felix Haurowitz, en cl Herman Eisen using precipitin meth-
ocis, was important in that it renclerecl unlikely that specific
antibody sites would simply be generated by folding around
an antigen template, as hacl been specified in the "instruc-
tion" theories of antibody formation, in most cletail by Pauling.
Towarc! the ens! of his stay at Roswell Park, Nisonoff
initiated experiments on the enzymatic cleavage of rabbit
antibodies, which contributed importantly to the growing
unclerstancling of their structure. Rodney Porter hac! shown
that two active univalent fragments, now known as Fab, couIcl
be proclucecl from each antibody molecule by digestion with
papain. Because papain is always user! in the presence of a
mercaptan, Nisonoff originally proposal that two steps, pro-
teolysis en cl clisulficle cleavage, were neeclecl to generate the
active univalent fragments. Accordingly, he repeated Porter's
experiment with a different enzyme, pepsin, which floes
not require activation by a mercaptan. Although the initial
premise was incorrect, as Nisonoff himself later pointer!
out, the experiment lecl to an even more interesting con-
clusion. Disulficle bond cleavage is not required to produce
the active univalent antibody fragments after papain cleav-
age, but it is required to produce univalent fragments after
limitecl digestion with pepsin. The explanation is that pa-
pain cleaves on the amino-terminal sicle of the single clisul-
fide bridge connecting the two heavy chains in rabbit IgG,
whereas pepsin cleaves on the carboxyI-terminal sicle of the
same bond, generating a single bivaTent fragment, F(ab')2.
Reduction of the inter-heavy chain bridge in the bivalent
fragment yields univalent Fab' fragments.
Nisonoff's studies provided critical insights into the na-
ture of the fragments proclucecl by digestion with papain
en cl their disposition in the intact antibody molecule. His
experiments with pepsin digestion implies! that the two frag-
OCR for page 165
ALFRED NISONOFF
165
meets containing the active site (Fate or Fab') are locater!
on the same sicle of the molecule, away from the Fc frag-
ment. The cleliberations by Porter's group that lecl to the
formulation of the polypepticle chain structure of IgG were
summarized by Julian FIeischman in a "citation classic" re-
view of the work. As FIeischman recallecI, Porter initially
favorer! the then popular cigar-shape mocle! in which the
two active fragments are clisposecl on either sicle of a cen-
tral Fc. However, this moclel was not easily reconcilecl with
Nisonoff's results with pepsin digestion en c! was therefore
abanclonecl in favor of the now familiar four-chain moclel
in which the two Fab fragments are on one sicle of the
molecule. Nisonoff's work also ciarifiec! the nature of chro-
matographic fractions I en cl II obtained by Porter after pa-
pain digestion of rabbit antibodies. The similar yielcl ini-
tially fount! for fractions I en c! II was fortuitous, the result
of charge heterogeneity in the antibody population en cl the
choice of column conditions. In fact, the more negatively
charger! antibody molecules were fount! to contain two Fab
fragments of type I en cl the more positively charged two
Fab fragments of type II.
The F(ab')2 fragment proclucec! by pepsin retains the
bivalence of the original antibody molecule en cl therefore
the ability to precipitate or agglutinate antigen. However, it
lacks the Fc fragment en c! will not bins! to cells expressing
Fc receptors, eliminating much unclesirecl "non-specific"
antibody bincling. The next logical step, taken by Nisonoff
just as he was moving from Roswell Park to a position as
associate professor of microbiology at the University of Illi-
nois, Urbana, was to show that the univalent Fab' fragments
generated by successive pepsin digestion and reduction could
be recombined into the bivalent F(ab')2 fragment by oxicia-
tion, allowing the creation of bivalent antibodies of mixecl
specificity. Such hybric! antibodies have hac! many practical
OCR for page 166
66
B I O G RA P H I C A L
EMOIRS
uses, for example, bringing a pharmacological agent into
contact with a particular cell type.
Throughout his career Nisonoff retained an interest in
the three-climensional structure of antibodies. As early as
the late 1950s this lecl to collaboration with Cecil Hall en cl
Henry Slater at the Massachusetts Institute of Technology
in an attempt to visualize the antibody molecule by elec-
tron microscopy. Although resolution was insufficient to
discern the shape, the ciata proviclecl a reasonable estimate
of the size of the molecule. Methods of X-ray crystallogra-
phy began to be applied to proteins in the 1960s. Recogniz-
ing the importance of applying these techniques to anti-
boclies, Nisonoff soon succeeclec! in obtaining crystals of
Fab fragments clerivecl from human IgG myeloma proteins.
Preliminary structural work was carried out in colIabora-
tion with Roberto Poijak's group, later more detailed stud-
ies carried out by PoIjak en cl others lecl to a cletailecl uncler-
stancling of the structure of the Fab fragment, inclucling
localization of the active site, the basic features of the Ig
foIcI, en cl the orientation of V en cl C domains.
In 1966 Nisonoff movecl from Urbana to the University
of Illinois College of Medicine in Chicago, where in 1969
he assumed the chair of the Department of Biological Chem-
istry. In Chicago he continual a fruitful collaboration with
Shelclon Dray, relating structural features of rabbit antibocI-
ies to genetic variations known as allotypy. In work using
Nisonoff's characteristic quantitative approach, they showocl
that the population of IgG molecules in a rabbit heterozy-
gous for allotype consists only of molecules displaying one
or the other allotypic determinant, but not both. Coming
on the heels of the proposal of the four-chain mocle! for
IgG, this finding suggested that the IgG molecule is sym-
metrical (i.e., with two iclentical heavy chains en cl two iclen-
tical light chains).
OCR for page 167
ALFRED NISONOFF
167
Thinking that quantitative immunochemical methods
wouIcl also be useful for investigating icliotypy (the unique
antigenic specificity possessed by incliviclual antibody mol-
ecuTes), Nisonoff embarked! on a series of studies that lair!
the groundwork for the wiclespreacl use of icliotypes as ge-
netic markers. IncleecI, studies of icliotypy were to occupy
him for the rest of his career. He cirew on his experience
with an tiboclies clirectecl against haptenic cle termin ants to
aciciress such questions as the relationship of the icliotypic
site of an antibody molecule to the antigen-bincling site. In
other studies Nisonoff aciciressecl such questions as the size
of the repertoire of antibocly-bincling sites en cl the relation-
sh~p of the ~ct~otyp~c site of an antibody molecule to the
antigen-binding site. For example, an important insight pro-
viclecl by Nisonoff, as well as others, was the recognition
that some icliotypic specificities can be sharer! by different
inclivicluals, so-callecl public icliotypes, en cl that these are
orobabIv encoded bv Caroline penes. The relationship be-
. . ~ .. . .. .
.. ~ ... . .
- J ~ - -- -J a- - a- --I - - 1-
tween icliotypes en c! genes encocling antibody V regions pro-
viclecl means for tracking clonal lines of B-lymphocytes.
In the 1960s evidence began to accumulate indicating
that a single germline gene conic! not encocle both the
variable en cl constant regions of an Ig heavy or light chain.
One of the critical finclings was proviclecl by Nisonoff, who
in collaboration with Hugh Fudenher~ shower! that IgG en c!
lglVl myeloma proteins ootalnect trom tne same patient had
iclentical icliotypes, en cl therefore iclentical V regions, as
was later confirmed! by sequence analysis. Because the C
regions of the gamma en cl mu chains must be encoclecl by
distinct genes, the V and C segments had to be specified by
separate genetic units.
He showocl that antibodies clirectecl against icliotypic cle-
terminants couIcl compete with hapten in bincling to anti-
bocly-combining regions. Nisonoff en c! l. DonaTc! Capra in a
T ~ ~ ~ , ~
- --a-- - -- -- ----- --a ---
~ . . ~ ~ . ~
OCR for page 168
68
B I O G RA P H I C A L
EMOIRS
collaboration that extenclec! over a number of years shower!
that icliotypes couIcl be clefinecl structurally en cl that icliotypic
differences between different strains of mice reflect genetic
variability. With Paul GottTieb, Nisonoff proviclec! evidence
that both heavy en cl light chains in an immunogIobulin
molecule are required for expression of the icliotype.
Nisonoff's work en c! that of others on icliotypy is summa-
rizecl in his presiclential aciciress for the American Associa-
tion of Immunologists meeting of 1991.
A major occupation en c! preoccupation of the later Chi-
cago years was the writing, together with John Hopper en cl
Susan Spring, of the monograph The Antibody Molecule
(1975), a monumental annotates! work providing a schol-
arly en cl comprehensive review of what we now call the B-
cell receptor. Choosing to review the fielcl at this time was a
reflection of Nisonoff's astute insight, for it proviclec! a cle-
finitive summary of the protein phase of molecular immu-
nology en cl set the stage for the genetic era that was soon
to follow. A clecacle later Nisonoff wrote an introductory
text of molecular immunology that showocl not only his
superb command of the subject but also his skill in present-
ing complex material. His extensive knowlecige en c! clear,
rigorous thinking macle him an excellent teacher both in
the laboratory en cl in the classroom.
In 1975 Nisonoff mover! to the Rosenstie! Research Center
at Brancleis University, where he helpecl to bring younger
colleagues to a group whose focus was research in immu-
nology. His own work continued to be centered on idiotypy.
Interestingly, he was recruited to Brandeis by Harlyn
Halvorson, then director of the Rosenstiel center, whose
father, H. Orin Halvorson, had brought Nisonoff to the
Microbiology Department at the University of Illinois, Ur-
bana, at the outset of his academic career.
Nisonoff's well-deserved reputation for critical scientific
OCR for page 169
ALFRED NISONOFF
169
insight en c! sounc! judgment meant that he was much sought
after to serve on review panels, advisory committees, en cl
eclitorial boards. In what may be a record, he served three
terms, once as chair, on the allergy en c! immunology stucly
section of the National Institutes of Health. He was presi-
clent of the American Association of Immunologists in 1990-
91. Even after giving up his research program in 1996,
Nisonoff continual as an Divisor to NIH en cl playocl a ma-
· . · · .
Or role In preparing a comprehensive report on current
knowlecige en c! future directions in immunology (Report of
the NIAID Task Force on Immunology, National Institutes
of Health, 1998~. Retirement was not easy for him, as he
misses! the give en c! take of the lab, but he remainec! as
sharp as ever en cl was always available for criticism en cl clis-
cussion with former colleagues.
One of Nisonoff's outstanding qualities was intellectual
honesty. Always direct and outspoken, he disliked pretense
in any form en cl was himself without any pretension. He
saw right to the heart of any question en c! brooked! no
fuzziness of thought. The high stanciarcis he set for himself
were a moclel for colleagues, as well as for the many stu-
clents he mentorecI. He pair! little attention to the external
trappings of fame, his or anyone else's. He was interested
in science for its own sake en cl was forever in pursuit of the
rigorous experiment that wouic! provicle an unambiguous
answer to a meaningful question.
Nisonoff's characteristic modesty is epitomized in the
format of his curriculum vitae in which his honors are bur-
ied in a section captioned "Other Data." He received the
Mecial of the Pasteur Institute in 1971, was a foreign corre-
sponclent of the Beigian Academy of Medicine in 1977, a
fellow of the American Academy of Arts en cl Sciences in
1982, en cl became a member of the National Academy of
Science in 1984.
OCR for page 170
170
B I O G RA P H I C A L
EMOIRS
As a young person Nisonoff hac! little exposure to the
visual arts or to music, but he came to love classical music
passionately en cl was a regular at Boston Symphony con-
certs. He lover! the works of many twentieth-century com-
posers but was generally not enamored of the newly com-
missionecl works that are often incluclecl in these concerts.
He was mover! to express this view in a letter sent to the
Boston Symphony just a few months before his cleath. Why,
he askocI, were new compositions so rarely playocl again
after their premiere? If they are worth hearing once, he
reasoned, surely they are worth hearing twice. As far as is
known, the question remained unanswered.
Nisonoff's sense of fun en c! goof! humor were legencI-
ary. In aciclition to music, he lovecl to play tennis en cl clicl so
regularly. He was invariably goocl for a lively discussion of
the current political scene. He hac! a strong lifelong sense
of social justice en cl always took the sicle of the unclerclog.
He quietly set about cloing what he couIcl to make his cor-
ner of the woric! a better place. After retirement from
Brancleis he coached kicis in math en cl recent immigrants
in English, and he was planning to take a course on teach-
ing English as a seconc! language.
Nisonoff was as honest in his human relationships as he
was in his science. To colleagues en cl students, as well as
family en c! friencis, he was loyal en c! committed. Although
he was clivorcecl from Sally in 1978, he continual to care
for her on a ciaily basis. He hacl a close relationship with his
chiTciren, Don en c! Lincia, en c! was a clevotec! grandfather.
He was the best friend of his younger sister, Lorraine. The
last clecacle of his life was immensely enriched by his friencI-
ship with Patricia Carella, who sharer! his love of music en c!
travel.
Al Nisonoff was one of a small number of investigators
whose accomplishments span the classical en c! moclern eras
OCR for page 171
ALFRED NISONOFF
171
in immunology. His work proviclec! critical insights into the
molecular nature of the antibody molecule en cl the genetic
basis for antibody diversity. He approached important bio-
Togical questions with the rigor of the chemist. His uncler-
stancling of this complex fielcl was as broacl as it was creep.
His publications s ten cl as a moclel of clear thinking en cl
· ~
vlslon.
OCR for page 172
172
B I O G RA P H I C A L
EMOIRS
SELECTED BIBLIOGRAPHY
1958
With D. Pressman. Heterogeneity and average combining constants
of antibody from individual rabbits. 7. Immunol. 80:417.
With D. Pressman. Heterogeneity of antibody sites in their relative
combining affinities for structurally related haptens. 7. Immunol.
81:126.
1959
With M. H. Winkler and D. Pressman. The similar specificity of the
combining sites of an individual antibody molecule. 7. Immunol.
82:201.
With C. E. Hall and H. S. Slayter. Electron microscopic observa-
tions of rabbit antibodies. 7. Biochem. Biophys. Cytol. 6:407.
1960
With F. C. Wissler and D. L. Woernley. Properties of univalent frag-
ments of rabbit antibody isolated by specific adsorption. Arch.
Biochem. Biophys. 88:241.
With F. C. Wissler, L. N. Lipman, and D. L. Woernley. Separation of
univalent fragments from the bivalent rabbit antibody molecule
by reduction of disulfide bonds. Arch. Biochem. Biophys. 89:230.
With F. C. Wissler and L. N. Lipman. Properties of the major com-
ponent of a peptic digest of rabbit antibody. Science 132:1770.
1961
With G. Markus and F. C. Wissler. Separation of univalent frag-
ments of rabbit antibody by reduction of a single, labile disulfide
bond. Nature 189:293.
With M. M Rivers. Recombination of a mixture of univalent anti-
body fragments of different specificity. Arch. Biochem. Biophys.
93:460.
1962
With J. L. Palmer and W. J. Mandy. Heterogeneity of rabbit anti-
body and its subunits. Proc. Natl. A cad. Sci. U. S. A. 48:49.
OCR for page 173
ALFRED NISONOFF
1963
173
With S. Dray. Contribution of allelic genes Ab4 and A be to forma-
tion of rabbit 7S 7-globulins. Proc. Soc. Exp. Biol. Med. 113:20.
1964
With A. M. Gilman and S. Dray. Symmetrical distribution of genetic
markers in individual rabbit 7-globulin molecules. Immunochem-
istryl:109.
1965
With R. Hong. Relative [abilities of the two types of interchain di-
sulf~de bonds of rabbit ~G-immunoglobulin. 7. Biol. Chem. 240:3883.
1968
With G. Rossi. Crystallization of fragment Fab of human IgG my-
eloma proteins. Biochem. Biophys. Res. Comm. 31:914.
With H. P. Avey, R. J. Poljak, and G. Rossi. Crystallographic data for
the Fab fragment of a human myeloma immunoglobulin. Nature
220:1248.
With S. Zappacosta and W. J. Mandy. Mechanism of cleavage of
rabbit IgG in two stages by soluble papain and reducing agent. 7.
Immunol. 100:1268.
1969
With H. Daugharty, J. E. Hopper, and A. B. MacDonald. Quantita-
tive investigations of idiotypic antibodies. I. Analysis of precipi-
tating antibody populations. 7. Exp. Med. 130:1047.
1970
With A. B. MacDonald. Quantitative investigations of idiotypic anti-
bodies. III. Persistence and variations of idiotypic specificities
during the course of immunization. 7. Exp. Med. 131:583.
With B. W. Brient. Quantitative investigations of idiotypic antibod-
ies. IV. Inhibition by specific haptens of the reaction of anti-
hapten antibody with its anti-idiotypic antibody. J. Exp. Med. 132:951.
With A. C. Wang, S. K. Wilson, J. E. Hopper, and H. H. Fudenberg.
Evidence for control of synthesis of the variable regions of the
heavy chains of immunoglobulins G and M by the same gene.
Proc. Natl. A cad. Sci. U. S. A. 66:337.
OCR for page 174
174
B I O G RA P H I C A L
1972
EMOIRS
With D. A. Hart, A.-L. Wang, and L. L. Pawlak. Suppression of
idiotypic specificities in adult mice by administration of anti-idiotypic
antibody. J. Exp. Med. 135:1293
With M. G. Kuettner and A.-L. Wang. Quantitative investigations of
idiotypic antibodies. VI. Idiotypic specificity as a potential ge-
netic marker for the variable regions of mouse immunoglobulin
polypeptide chains. J. Exp. Med. 135:579.
With R. J. Poljak, L. M. Amzel, H. P. Avey, and L. N. Becka. The
structure of Fab' "New" at 6 A resolution. Nature New Biol. 235:137.
1973
With L. L. Pawlak, E. B. Mushinski, and M. Potter. Evidence for the
linkage of the IGCH locus to a gene controlling the idiotypic
specificity of anti-'azophenylarsonate antibodies in strain A mice.
J Exp. Med. 137:22.
1974
With K. Eichmann and A. S. Tung. Linkage and rearrangement of
genes encoding mouse immunoglobulin heavy chains. Nature 250:509.
1975
With J. D. Capra and A. S. Tung. Structural studies on induced
antibodies with defined idiotypic specificities. I. The heavy chains
of anti-p-azophenylarsonate antibodies from A/J mice bearing a
cross-reactive idiotype. 7. Immunol. 114:1548.
With J. E. Hopper and S. B. Spring. The Antibody Molecule. New
York: Academic Press.
1977
With S.-T. Ju and A. Gray. Frequency of occurrence of idiotypes
associated with anti-p-azophenylarsonate antibodies arising in mice
immunologically suppressed with respect to a cross-reactive idiotype.
7. Exp. Med. 145:540.
With J. A. Laskin, A. Gray, N. R. Klinman, and P. G. Gottlieb. Segre-
gation at a locus determining an immunoglobulin genetic marker
for the light chain variable region affects inheritance of expres-
sion of an idiotype. Proc. Natl. A cad. Sci. U. S. A. 74:4600.
OCR for page 175
ALFRED NISONOFF
1981
175
With A. R. Brown and E. Lamoyi. Relationship of idiotypes of the
anti-~azophenylarsonate antibodies of A/J and BALB/c mice. 7.
Immunol. 126: 1 268.
1984
Introduction to Molecular Immunology. Sunderland, Mass.: Sinauer
Associates.
1991
American Association of Immunologists Presidential Address. Idiotypes:
Concepts and applications. 7. Immunol. 147:2429.
Representative terms from entire chapter:
alfred nisonoff
