CDS, and the T cell receptor. Dr. Bottomly's labora- 
tory has characterized CD45 in T cell development 
in the thymus. These studies show that maintenance 
of the CD45RA high-molecular- weight isoform cor- 
relates with positive selection; and its loss, with 
entry of the developing T cell into a pathway leading 
to apoptosis. This suggests that retention of CD45 in 
the isoform might allow developing T cells to sur- 
vive, and this is being tested using transgenic mice. 
Dr. Bottomly is also Associate Professor of Im- 
munobiology at Yale University School of Medi- 
cine and Associate Professor of Biology at Yale 
University. 
Articles 
Carding, S.R., Lu, D.D., and Bottomly, K. 1992. A 
polymerase chain reaction assay for the detection 
and quantitation of cytokine gene expression in 
small numbers of cells. / Immunol Methods 
151:277-287. 
Dianzani, U., Redoglia, V., Malavasi, F., Bragardo, 
M., Pileri, A., Janeway, C.A., Jr., and Bottomly, 
K. 1992. Isoform-specific associations of CD45 
with accessory molecules in human T lympho- 
cytes. Eur J Immunol 22:365-371. 
Dobbcr, R., Hertogh-Huijbregts, A., Rozing, J., Bot- 
tomly, K., and Nagelkerken, L. 1992. The in- 
volvement of the intestinal microflora in the ex- 
pansion of CD4^ T cells with a naive phenotype in 
the periphery. Dev Immunol 2:141-150. 
Eichelberger, M., Allan, W., Carding, S.R., Bot- 
tomly, K., and Doherty, P.C. 1991- Activation 
status of the CD4~8" yb-T cells recovered from 
mice with influenza pneumonia. / Immunol 
147:2069-2074. 
Hobbs, M.V., Ernst, D.N., Torbett, B.E., Glasebrook, 
A.L., Rehse, M.A., McQuitty, D.N., Thoman, M.L., 
Bottomly, K., Rothermel, A.L., Noonan, D.J., and 
Weigle, W.O. 1991. Cell proliferation and cyto- 
kine production by CD4^ cells from old mice. / 
Cell Biochem 46:312-320. 
Luqman, M., Greenbaum, L., Lu, D., and Bottomly, 
K. 1992. Diff'erential effect of interleukin 1 on 
naive and memory CD4* T cells. Eur J Immunol 
22:95-100. 
McVay, L.D., Hayday, A.C., Bottomly, K., and Card- 
ing, S.R. 1991 . Thymic and extrathymic develop- 
ment of human 7/5 T cells. Curr Top Microbiol 
Immunol 173:57-63. 
Murray, J. S., Pfeiffer, C, Madri,J., and Bottomly, K. 
1992. Major histocompatibility complex (MHC) 
control of CD4 T cell subset activation. II. A sin- 
gle peptide induces either humoral or cell- 
mediated responses in mice of distinct MHC geno- 
type. Eur J Immunol 22:559-565. 
Pfeiff^er, C, Murray, J., Madri, J., and Bottomly, K. 
1991. Selective activation of Thl- and Th2-like 
cells in vivo — response to human collagen IV. 
Immunol Rev 123:65-84. 
Smith, A.L., Banhold, S.W., de Souza, M.S., and Bot- 
tomly, K. 1991 ■ The role of gamma interferon in 
infection of susceptible mice with murine corona- 
virus, MHV-JHM. Arch Virol \ 2\ -.89 -\0Q. 
MOLECULAR GENETICS OF THE HLA AND CYTOKINE SYSTEMS 
David D. Chaplin, M.D., Ph.D., Associate Investigator 
Research in Dr. Chaplin's laboratory is centered 
on two areas: 1) analysis of the structure and func- 
tion of the human major histocompatibility com- 
plex (MHC) and 2) characterization of the interleu- 
kin- 1 (IL-1) family of molecules. 
Structure and Function of the Human MHC 
The MHC contains genes encoding the cell sur- 
face glycoproteins that present peptide antigens to 
a/|8 T lymphocytes. The human MHC, or human leu- 
kocyte-associated antigen (HLA) complex, has also 
been recognized to determine susceptibility to 
more than 200 different diseases. Because linkage 
disequilibrium is strong within the MHC, the molec- 
ular basis for most of these HLA-associated illnesses 
has been difficult to identify definitively. The HLA 
complex is recognized to span more than 4 million 
base pairs of DNA. Approximately 60 MHC genes 
have been defined, and it is currently estimated that 
an additional 40-100 undiscovered genes map 
within the complex. Understanding normal MHC 
immune function and the basis for many of the HLA- 
linked human diseases depends on defining the 
complete gene content of the MHC. 
To obtain the nucleic acid reagents for definition 
of the gene content of the HLA region. Dr. Chaplin's 
laboratory has isolated nearly the entire human 
MHC as a collection of overlapping molecular 
316 
