DEVELOPMENT OF 78 T CELLS 
SusuMU TONEGAWA, PH.D., Itivesttgator 
Dr. Tonegawa's major research interest continues 
to be the newly discovered T cell receptor (TCR) 78 
and T cells bearing this TCR. Because nothing was 
known about this type of TCR and T cells when the 
TCR 7 gene was discovered in Dr. Tonegawa's labo- 
ratory in 1984, the research has been progressing 
in a reverse direction— from the gene to the pro- 
tein, from the protein to the cell, and from the cell 
to the function. The function of 76 T cells is still un- 
known. However, much information has been 
learned during the past year about the diversity, tis- 
sue distribution, development, and specificity of 
these T cells, and some plausible roles for these T 
cells are emerging. 
L Preparing Monoclonal Antibodies Reactive with 
Mouse 78 TCR. 
Monoclonal antibodies directed against the na- 
tive receptor are useful in the study of the nature of 
-y6 TCR and the role of -y6 T cells. By immunizing 
Armenian hamsters with the 78 TCR-CD3 complex 
partially purified from a lysate of a 76 T hybridoma, 
KN6, Dr. Tonegawa's laboratory prepared three 
anti-78 TCR monoclonal antibodies: 3A10, specific 
for a C7 constant region determinant; 8D6, specific 
for V^4- and Vg^-encoded 78 TCR; and 5C10, spe- 
cific for a KN6 TCR idiotope. 
IL Distribution of 78 T Cells. 
The availability of the staining anti-78 monoclo- 
nal antibody allowed Dr. Tonegawa's laboratory to 
enumerate 78 T cells in developing thymus and pe- 
ripheral lymphoid organs by flow cytometry and 
immunohistochemistry As the earlier immuno- 
precipitation and molecular genetic analyses sug- 
gested, 78 T cells appear one to two days earlier 
(day 14.5 of gestation) in the fetal thymus than aP 
T cells, but compose no more than a few percent of 
the total thymocytes or splenic T cells throughout 
the animal's life. Most of these T cells do not ex- 
press CD4 or CDS. By contrast, following the re- 
ports of the occurrence of 78 T cells in epidermis 
and gut epithelia. Dr. Tonegawa's laboratory dem- 
onstrated that many organs carry 78 T cells that are 
frequently in association with their epithelial cells. 
These organs include large intestine, tongue, stom- 
ach, uterus, and vagina. Although some a(3 T cells 
are also present in association with the epithelia of 
some of these organs, the majority of CD3^ in- 
traepithelial lymphocytes are clearly 78 T cells, sug- 
gesting a role for these T cells in the surveillance of 
epithelial cells. Dr. Tonegawa's laboratory refers to 
these 78 T cells as intraepithelial lymphocytes (lEL); 
the initial of each organ is used to designate various 
lEL subpopulations, such as i-IEL, s-IEL, r-IEL, and 
t-IEL for the lEL in intestine, skin, reproductive or- 
gans, and tongue, respectively. 
III. 78 T Cell Subpopulations with Virtually No TCR 
and Abundant TCR Diversity. 
The 78 T cells are composed of several different 
subpopulations, which are characterized by gene 
segments utilized to encode their TCR, by widely 
different degrees of TCR variability, by preferred lo- 
calization in specific anatomical sites, and by the 
timing of their appearance in the developing thy- 
mus. Thus, following the demonstration that virtu- 
ally all s-IEL 78 TCR are encoded by V^jCj7 and 
VjDy^S genes with no sequence diversity, Dr. Tone- 
gawa's laboratory demonstrated that the TCR of vir- 
tually all r-IEL and t-IEL are encoded by VJjCj7 
with no sequence diversity and by the 8 gene 
whose nucleotide sequence is identical to that of 
the 8 gene encoding the s-IEL 8-chain. Further- 
more, Dr. Tonegawa's laboratory demonstrated that 
most 78 thymocytes that appear early in fetal devel- 
opment (i.e., day 14-16 of gestation) and disappear 
thereafter express the same, undiversified TCR as 
that expressed on s-IEL. They also demonstrated 
that this wave of 78 thymocytes is followed by an- 
other wave that peaks around birth and is com- 
posed of T cells bearing the same, undiversified 78 
TCR as that present on most r-IEL and t-IEL. In con- 
trast, the TCR expressed on adult 78 thymocytes 
and on the 78 T cells of adult lymphoid organs are 
diverse, exhibiting both combinatorial and junc- 
tional diversity. The diversity of the i-IEL 76 TCR, on 
the other hand, seems to be intermediate, because 
the preferential utilization of V^jCj7 genes virtu- 
ally precludes the combinatorial diversity of their 
7-chains. 
rv Silencer Model of a3 and 78 T Cell 
Development. 
The discovery of 78 T cells raises the issue of 
their developmental relationship with a(3 T cells. It 
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