Although class I MHC proteins were first identified over
50 years ago, their function has only been understood in
detail in the past two decades. The three-dimensional
structure of the human class I molecule HLA-A2 represented
a landmark achievement in the field (Bjorkman
et al., 1987a,b). The structure revealed the presence of a
binding cleft suggesting antigen binding capability and
offered tantalizing evidence of the nature of peptides
bound. Shortly thereafter, bacterially produced recombinant
class I proteins were re-folded with synthetic peptides
which, upon crystallographic analysis, elucidated the
molecular details of peptide binding in the cleft (Garrett
et al., 1989). In addition to their importance for understanding
T-cell recognition, these studies formed the
basis for developing class I MHC tetramers, reagents with
widespread current use in identifying antigen-specific
CD8 T cells, as will be discussed elsewhere in this
volume.