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TitleAdvances in Immunology [Vol 28] - F. Dixon, H. Kunkel (AP, 1979) WW
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Page 2

ADVANCES I N

I m m u n o l o g y

V O L U M E 28

Page 267

254 R. J. WINCHESTER AND H. G. KUNKEL

A third approach involves short-term cultivation of peripheral blood
mononuclear cells with a mitogen, pokeweed (Winchester et al.,
197513) or phytohemagglutinin (Colombani et al., 1977a). The result-
ing B cells with a variable addition of Ia-bearing T cells are examined
by cytotoxicity or immunofluorescence. In the author’s laboratory the
procedure involves incubation with the alloantiserum, washing, and
incubation with a mixture of rhodamine-tagged antihuman IgG and
fluorescein-tagged heteroanti-Ia. The coincidence of both fluoro-
chromes indicates a positive reaction. The disadvantage of a culture
step makes this method suited for more specialized applications where
the inherent precision is required.

The high level of isolated T cells that express Ia after cultivation
with pokeweed mitogen (KO et al., 197913) suggests that this could be a
valuable alternative approach, with obvious applications in instances
of B cell deficiency.

Monocyte contamination (which is involved in essentially all proce-
dures, especially when nonnormal subjects are used) presents a major
problem because the majority of monocytes have abundant Ia alloan-
tigens (Winchesteret al., 1975a, 1976; Jones et al., 1975; Albrechtsen et
al., 1977a). However, although the Ia alloantigen specificities parallel
those on the B cells, they are frequently not killed under conditions
that usually result in satisfactory B cell cytotoxic typing (Cicciarelli et
al., 1978; Drew et nl., 1978). This variable, cytotoxicity-negative
absorption-posi tive phenomenon has the effect of diminishing the per-
centage of maximum cells that can be killed in a way that is difficult to
control. In addition, the presence on monocytes of differentiation al-
loantigens unrelated to the MHC (Claas et al., 1979) further em-
phasizes the need for their identification and exclusion from typing
s y s tern s .

B. COMPLEXITY OF Ia ALLOANTIGENS
The objectives of studies on the Ia alloantigens fall into four catego-

ries: ( a ) to refine the specificity of the reagent alloantisera in order to
establish a relation to discrete single gene products; ( h ) to characterize
the molecular basis of the discrete alloantigen specificities; (c) to
define the genetic organization of the structural genes; and (d ) to relate
the structural genes to other genes mapping in the same region. It is
becoming evident that the combination of newer serologic, genetic,
and chemical studies is enlarging the concept of the human la alloan-
tigens into a system at least as complex as that of the murine I region.

Page 268

THE HUMAN Ia SYSTEM 255

TABLE VIP
DRw GENE FREQUENCIES IN DIFFERENT POPULATIONS (%) AS DETERMINED

IN THE VII INTERNATIONAL WORKSHOP ON HISTOCOMPATIBILITY TESTING

North
European American American African American

Allele Caucasoids Caucasoids Blacks Blacks Japanese Indians

DRwl 6.2 5.2 7.3 - 4.5 -
DRw2 11.2 13.9 13.8 8.7 16.5 8.4
DRw3 8.9 11.8 12.4 11.7 - 9.1
DRw4 7.8 16.5 7.2 3.5 14.4 21.5
DRw5 15.1 11.9 15.4 7.4 5.4 6.0
DRw6 8.6 11.5 19.1 9.9 6.7 5.9
DRw7 15.6 12.4 12.0 6.6 - 3.7
WIA8 5.6 4.2 7.5 7.2 7.2 12.9
Blank 21.1 12.6 5.3 45.0 45.3 32.5
N 334 273 110 77 164 69

b

~ ~~~~~~~ ~

From “Histocompatibility Testing 1977” (1978) (W. F. Bodmer, J. R. Batchelor,

Alleles indicated-are not present in this population.
J. G. Bodmer, H. Festenstein, and, P. J. Morris, eds.). Munksgaard, Copenhagen.

1 . Relationship of l a Specijicities to MLC Determinants
Definition of DR Specijicities. As an outgrowth of the earlier use of

Ia allosera in MLC inhibition experiments (Ceppellini et al., 1971;
van Leeuwen et al., 1973), the first phase of characterizing reagent
specificities emphasized those sera that had a clear relationship to the
HLA-D determinants (van Rood et al., 1975; Winchester et al., 197513;
Legrand and Dausset, 1975; Terasaki et al., 1975; Walford et al., 1976).
The general correlation between the specificities of certain Ia alloan-
tisera and HLA-D determinants was confirmed (Albrechtsen et al.,
1977b; Park et al., 1977; van Rood et al., 1977; Walford et al., 1977)
and formed one of the central contributions of the VIIth International
Workshop. Both cluster analysis (Bodmer et al., 1978b; Bodmer, 1978)
and segregation of MLC and Ia specificities on the same haplotype in
family studies (Lamm et al., 1978) provided further support. The term
“DR” was proposed to designate the relationship of the Ia specificities
to the HLA-D locus alleles defined by MLC testing.

In the VII Workshop eight DR specificities were delineated. Of
these, if any two are excluded from analysis, the frequencies of the
remaining six fit well with a segregant series of six alleles at a single
locus in Hardy-Weinberg equilibrium (Pickbourne et al., 1978). Gene
frequencies of the DR types calculated from these assumptions are
shown in Table VII. From the available data it was not considered

Page 534

CONTENTS OF PREVIOUS VOLUMES 52 1

Amino Acid Substitution and the
Antigenicity of Globular Proteins

MORRIS REICHLIN

The H-2 Major Histocompatibility Complex
and the I Immune Response Region:
Genetic Variation, Function, and
Organization

. CHELLA S. DAVID
DONALD c. SHREFFLER AND

Delayed Hypersensitivty in the Mouse
ALFRED J. CROWLE

SUBJECT INDEX

Volume 21

X-Ray Diffraction Studies of
lmmunoglobulins

ROBERTO J. POLJAK

Rabbit Immunoglobulin Allotypes:
Structure, Immunology, and Genetics

THOMAS J. KINLYT

Cyclical Production of Antibody as a
Regulatory Mechanism in the Immune
Response

Thymus-Independent 8-Cel I Induction and
Pa ral ysis

WILLIAM 0. WIECLE

ANTONIO COUTINHO AND
GORAN MOLLER

SUBJECT INDEX

Volume 22

The Role of Antibodies in the Rejection and
Enhancement of Organ Allografts

CHARLES B. CARPENTER,
ANTHONY J. F. D'APICE, AND
ABUL K. ABBAS

HARVEY R. COLTEN
Biosynthesis of Complement

Graft-versus-Host Reactions: A Review
STEPHEN c. GREBE AND
J. WAYNE STREILEIN

Cellular Aspects of Immunoglobulin A
MICHAEL E. LAMM

Secretory Anti-Influenza Immunity
YA. s. SHVARTSMAN AND
M. P. Z m o V

SUBJECT INDEX

Volume 23

Cellular Events in the IgE Antibody
Response

KIMISHICE ISHIZAKA

Chemical and Biological Properties of
Some Atopic Allergens

T. P. KING

Human Mixed-Lymphocyte Culture
Reaction: Genetics, Specificity, and
Biological Implications

Bo DUPONT, JOHN A. HANSEN,

Immunochemical Properties of Glycolipids
and Phospholipids

AND EDMOND J. YUNIS

DONALD M. MARCUS AND
GERALD A. SCHWARTINC

SUBJECT INDEX

Volume 24

The Alternative Pathway of Complement
Activation

0. GOTZE AND H. J.
MULLER-EBERHARD

Membrane and Cytoplasmic Changes in B
Lym p hocytes Induced by Liga ndcSurface
Immunoglobulin Interaction

EMIL R. UNANUE

HOWARD B. DICKLER

GEORGE F. SCHREINER AND

Lymphocyte Receptors for Immunoglobulin

Ionizing Radiation and the Immune
Response

ROBERT E. ANDERSON AND
NOEL L. WARNER

SUBJECT INDEX

Page 535

522 CONTENTS OF PREVIOUS VOLUMES

Volume 25

Immunologically Privileged Sites
CLYDE F. BARKER AND
R. E. BILLINCHAM

Major Histocompatibility Complex
Restricted Cell-Mediated Immunity

GENE M. SHEARER AND
ANNE-MARIE SCHMITT-VERHULST

DAVID L. GASSER

MICHAEL POTTER

L. CHESS AND S. F. SCHLOSSMAN

Current Status of Rat lmmunogenetics

Antigen-Binding Myeloma Proteins of Mice

Human lymphocyte Subpopulations

SUBJECT INDEX

Volume 26

Anaphylatoxins: C3a and C5a

MULLER-EBERHARD
TONY E. HUCLI AND HANS J ,

H-2 Mutations: Their Genetics and Effect on
Immune Functions

JAN KLEIN

The Protein Products of the Murine 17th
Chromosome: Genetics and Structure

ELLEN s. VITETTA AND J. DONALD
CAPRA

Expression and Function of ldiotypes on
Lym phoc ytes

K. EICHMANN

NOLAN H. SICAL AND NORMAN R.
KLINMAN

The 6-Cell Clonotype Repertoire

SUBJECT INDEX

Volume 27

Autoimmune Response to Acetylcholine
Receptors in Myasthenia Gravis and Its
Animal Model

JON LINDSTROM

MHC-Restricted Cytotoxic T Cells: Studies
an the Biological Role of Polymorphic
Major Transplantation Antigens
Determining T-cell Restriction-Specificity,
Function, and Responsiveness

ROLF M. ZINKERNACEL AND PETER
C. DOHERTY

Murine Lymphocyte Surface Antigens
IAN F. c. MCKENZIE AND TERRY
POTTER

The Regulatory and Effector Roles of
Eosi nophi Is

PETER F. WELLER AND EDWARD J.
GOETZL

SUBJECT INDEX

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