THE MECHANISMS OF PEPTIDE EXCHANGE AND BETA(2)-MICROGLOBULIN EXCHANGEON CELL-SURFACE L(D) AND K-B MOLECULES ARE NONCOOPERATIVE

It has previously been shown that the presence of exogenous beta(2)-mi croglobulin (beta(2)m) can dramatically enhance the binding of exogeno us peptide to cell surface class I MHC. However, the mechanism by whic h this enhancement takes place is unknown, Two models have been propos ed to explain this phenomenon, In the first model, the exchange of pep tide and the exchange of beta(2)m are cooperative processes. In the al ternative model, beta(2)m stabilizes free class I heavy chains to incr ease the total number of peptide binding sites available. In this repo rt, we have examined the relationship between peptide exchange and bet a(2)m exchange, Comparisons of L(d) and K-b complexes formed with pept ides possessing widely disparate affinities revealed a reciprocal corr elation between the peptide off-rate and the rate of beta(2)m exchange , This result indicates that peptide exchange and beta(2)m exchange ar e noncooperative processes that may, in fact, antagonize one another, These findings provide the first demonstration of peptide-specific inf luences on the rate of beta(2)m exchange and suggest that exogenous be ta(2)m promotes peptide binding by maintaining class 1 heavy chains in a peptide-receptive state.