CD8 ENHANCES FORMATION OF STABLE T-CELL RECEPTOR MHC CLASS-I MOLECULECOMPLEXES

T-CELL antigen receptors (TCR) generally interact with moderate affini ty with the complex formed by major histocompatibility complex (MHC) m olecules and foreign peptides(1-7), MHC/TCR recognition is followed by the generation of a signal to the T cell through a monomorphic multic omponent system that includes the CD3 complex and accessory molecules such as CD4 and CD8, The interaction between the extracellular domains of MHC and TCR molecules(1-7), and the interaction of MHC and CD4/CD8 molecules(8-10), have been considered to occur independently of one a nother. We report here that the affinity of CD8 dimers for MHC class I molecules is independent of haplotype and peptide content, and that t he affinity of the TCR for its specific ligand is enhanced through a r educed 'off' rate in the presence of either CD8 alpha alpha homo- or C D8 alpha beta heterodimers. Moreover, CD8 seems to help recognition of the specific MHC-peptide complex either by guiding an energetically f avourable docking of TCR onto MHC, or by inducing conformational chang es in the MHC complex that can augment the TCR/MHC-peptide interaction . CD8 should therefore be considered as an active participant in the T -cell recognition complex, rather than simply as an accessory molecule .