achieving a molecular definition of a minor histo- 
compatibility antigen. The group had earlier suc- 
ceeded in identifying a short peptide, encoded in 
the mitochondrial genome, which is the maternally 
transmitted component of this antigen. This pep- 
tide is presented on the cell surface by a major his- 
tocompatibility class I molecule, Hmt. This year sev- 
eral class I genes from the chromosomal region that 
encodes Hmt were defined, cloned, sequenced, and 
characterized. One of these, R4B2, is an excellent 
candidate for the Hmt gene. Hmt is the first non- 
classical class I molecule known to present an iden- 
tified self peptide. 
Experiments in the laboratory of Associate Inves- 
tigator Richard G. Cook, Ph.D. (Baylor College of 
Medicine) are focused on the biochemical struc- 
ture, regulation of expression, and function of the 
class I MHC alloantigens encoded by the Q and TL 
region genes. Northern blot analyses, two-dimen- 
sional gel, and amino acid sequence data have re- 
vealed that two Q region genes encode the Qa-2 an- 
tigen family Some strains express Q7 and Q9, while 
others express only Q9- Certain anti-Qa-2 monoclo- 
nal antibodies also were found to induce lympho- 
cyte activation. Analysis of the 5' region of a TL 
gene suggests that there are both positive and neg- 
ative regulatory motifs that control the tissue-spe- 
cific expression of TL antigens. 
Assistant Investigator C. Geoffrey Davis, Ph.D. 
(University of California at San Francisco) and his 
colleagues are studying the trafficking of class I 
products of the human MHC. In the past year the 
laboratory has made advances in their efforts to es- 
tablish a model system in which to study endocyto- 
sis of these surface molecules. Certain aspects of 
this system have revealed intriguing features of in- 
tracellular processing that are also under investiga- 
tion. Finally, analysis of chimeric molecules has re- 
vealed that cytoplasmic domains not only contain 
signals sufficient for directing surface molecules 
into the endocytosis pathway but also play a role in 
determining whether they subsequently recycle to 
the surface. 
The genetic pathways of early lymphocyte devel- 
opment and the aberrancies that result in malig- 
nancy are the concern of Associate Investigator 
Stanley J. Korsmeyer, M.D. (Washington University) 
and his colleagues. Highly characteristic transloca- 
tions between unrelated chromosomes frequently 
occur in malignant cells of human lymphomas and 
leukemias. This event may juxtapose the genes of 
immunoglobulin or T cell receptors with new puta- 
tive cancer genes. One such gene, Bcl-2, isolated 
from human follicular lymphoma, was shown to ex- 
tend the survival of cells. A deregulated form of 
Bcl-2 was introduced into the genetic material of 
mice. These animals develop B cell neoplasms, pro- 
viding a prospective role for this translocation in 
tumor development. Candidates for cancer-promot- 
ing genes have been identified in T cell tumors. Ap- 
proaches are being developed also to characterize 
large expanses of the human genome to identify 
disease loci that lie at considerable distances from 
known genes. 
The laboratory of Investigator Owen N. Witte, 
M.D. (University of California at Los Angeles) deals 
with two interrelated problems: cell growth regula- 
tion and the differentiation of blood cells. The re- 
search is focused on two major areas: 1) the devel- 
opment of techniques that will allow growth and 
manipulation of specific types of blood cells and 2) 
the investigation of the function of genes found in 
certain human leukemias, such as Philadelphia 
chromosome-positive acute lymphocytic leukemia 
and chronic myelogenous leukemia, in which the 
ABL oncogene is changed by chromosome rear- 
rangement, leading to abnormal growth control. 
The long-range goal of this research is to increase 
understanding of the way in which these oncogene 
products stimulate and regulate abnormal cell 
growth and to use this information to understand 
the control of normal cell growth. 
Complement is a recognition and effector system 
that evolved to protect the host from infectious or- 
ganisms. It accomplishes this task by attaching to 
the foreign agent and by promoting the inflamma- 
tory response. The bound complement compo- 
nents serve as ligands for receptors on peripheral 
blood cells and tissue macrophages. This process 
must be carefully regulated in order that compo- 
nents become attached to foreign and not self tis- 
sue. Consequently much of the regulation of the 
complement system centers on controlling activa- 
tion of complement at the critical step in which the 
fragments that can attach to cells are generated. 
The laboratory of Investigator John P Atkinson, 
M.D. (Washington University) has been instrumen- 
tal in identifying and characterizing such regulatory 
molecules. Specifically, these regulatory and recep- 
tor glycoproteins were found to belong to a new 
multigene family of functionally, structurally, and 
genetically related molecules whose structural 
genes are located on the long arm of human chro- 
mosome 1. 
In the complement system a cascade of serum 
proteins is activated by foreign antigens and func- 
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