T cell antigen receptors (TCRs) on mature T cells react with peptide a
ntigens presented by self-MHC proteins and also frequently cross-react
with foreign MHC proteins. The fundamental question whether MHC react
ivity is inherent in the germline TCR sequences or is imposed by thymi
c selection was addressed here by inducing nonselective maturation of
immature thymocytes in the absence of MHC molecules. MHC reactivity in
the preselection repertoire is very high, but no higher than in the n
ormal repertoire. cross-reactivity of clones with multiple MHC molecul
es occurred to a similar extent in the preselection and MHC-selected r
epertoires. The results establish the MHC reactivity of the germline T
CR repertoire, indicate the minimum fraction of immature thymocytes th
at must undergo negative selection, and suggest that some TCR-MHC cont
acts may be conserved.