T Lymphocyte Ontogeny and Specificity 
therefore set up as mimics of the foreign anti- 
genic world, predicting the antigenic universe 
that the immune system will encounter after thy- 
mic maturation. 
Class I MHC Antigen Presentation 
The class I heavy and light chains have amino- 
terminal signal sequences so that they are made 
on membrane-bound ribosomes and assemble in 
the endoplasmic reticulum. Many of the peptide 
antigens that they complex with and present to 
cytotoxic T cells, however, derive from internal 
viral proteins that are made in the cytoplasm on 
free ribosomes. It seems likely that there is a pep- 
tide transporter located in a pre-Golgi membrane 
that allows the transfer of unfolded molecules or 
peptide fragments from the cytoplasm into the 
compartment occupied by nascent class I mole- 
cules. Because of the nature of class I-restricted 
antigen presentation, the readily and cheaply 
available protein antigens such as egg proteins 
and serum proteins could not be used to stimu- 
late a cytotoxic response. We overcame this 
problem by using the genes for chicken ovalbu- 
min and (8-galactosidase transfected into mouse 
cells to generate such class I-restricted re- 
sponses. By this entirely artificial procedure, we 
converted these antigens into endogenously syn- 
thesized mouse proteins and were readily able to 
stimulate a class I-restricted cytotoxic response. 
This system has been used to study how antigen 
gains access to the class I pathway of antigen pro- 
cessing and presentation. Soluble protein antigen 
can be introduced into the cytoplasm and then 
into the class I antigen-processing pathway by the 
osmotic lysis of pinosomes or by the uptake of 
acid-sensitive liposomes that fuse with endoso- 
mal membranes. We have used these systems to 
study the kinetics of antigen breakdown and pre- 
sentation and to ask what degradation systems are 
involved in antigen processing for class I- 
restricted presentation. 
44 
