THE MHC REACTIVITY OF THE T-CELL REPERTOIRE PRIOR TO POSITIVE AND NEGATIVE SELECTION

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.